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Sample records for dynamics regulate multiple

  1. Safe Dynamic Multiple Inheritance

    DEFF Research Database (Denmark)

    Ernst, Erik

    2002-01-01

    Multiple inheritance and similar mechanisms are usually only supported at compile time in statically typed languages. Nevertheless, dynamic multiple inheritance would be very useful in the development of complex systems, because it allows the creation of many related classes without an explosion...... in the size and level of redundancy in the source code. In fact, dynamic multiple inheritance is already available. The language gbeta is statically typed and has supported run-time combination of classes and methods since 1997, by means of the combination operator '&'. However, with certain combinations...

  2. Multiple time scale dynamics

    CERN Document Server

    Kuehn, Christian

    2015-01-01

    This book provides an introduction to dynamical systems with multiple time scales. The approach it takes is to provide an overview of key areas, particularly topics that are less available in the introductory form.  The broad range of topics included makes it accessible for students and researchers new to the field to gain a quick and thorough overview. The first of its kind, this book merges a wide variety of different mathematical techniques into a more unified framework. The book is highly illustrated with many examples and exercises and an extensive bibliography. The target audience of this  book are senior undergraduates, graduate students as well as researchers interested in using the multiple time scale dynamics theory in nonlinear science, either from a theoretical or a mathematical modeling perspective. 

  3. Multiplicities and parton dynamics

    International Nuclear Information System (INIS)

    Knuteson, R.O.

    1987-01-01

    The production of strongly interacting particles from the annihilation of electrons and positrons at high energies is studied, with emphasis on the multiplicity, or number, of particles produced. A probabilistic branching model based on the leading log approximation in QCD is formulated to predict the evolution of particle number with the energy of collision. Direct integration of a master equation for the probabilities allows a comparison to the experimentally observed particle distribution. The production of strongly interacting particles from proton-antiproton collisions is also considered. A model for the production of particles from parton-parton collisions is presented and the growth in multiplicity with energy demonstrated

  4. A Nonlinear Dynamic Approach Reveals a Long-Term Stroke Effect on Cerebral Blood Flow Regulation at Multiple Time Scales

    Science.gov (United States)

    Hu, Kun; Lo, Men-Tzung; Peng, Chung-Kang; Liu, Yanhui; Novak, Vera

    2012-01-01

    Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at > = 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary

  5. The Drosophila nerfin-1 mRNA requires multiple microRNAs to regulate its spatial and temporal translation dynamics in the developing nervous system.

    Science.gov (United States)

    Kuzin, Alexander; Kundu, Mukta; Brody, Thomas; Odenwald, Ward F

    2007-10-01

    The mRNA encoding the Drosophila Zn-finger transcription factor Nerfin-1, required for CNS axon pathfinding events, is subject to post-transcriptional silencing. Although nerfin-1 mRNA is expressed in many neural precursor cells including all early delaminating CNS neuroblasts, the encoded Nerfin-1 protein is detected only in the nuclei of neural precursors that divide just once to generate neurons and then only transiently in nascent neurons. Using a nerfin-1 promoter-controlled reporter transgene, replacement of the nerfin-1 3' UTR with the viral SV-40 3' UTR releases the neuroblast translational block and prolongs reporter protein expression in neurons. Comparative genomics analysis reveals that the nerfin-1 mRNA 3' UTR contains multiple highly conserved sequence blocks that either harbor and/or overlap 21 predicted binding sites for 18 different microRNAs. To determine the functional significance of these microRNA-binding sites and less conserved microRNA target sites, we have studied their ability to block or limit the expression of reporter protein in nerfin-1-expressing cells during embryonic development. Our results indicate that no single microRNA is sufficient to fully inhibit protein expression but rather multiple microRNAs that target different binding sites are required to block ectopic protein expression in neural precursor cells and temporally restrict expression in neurons. Taken together, these results suggest that multiple microRNAs play a cooperative role in the post-transcriptional regulation of nerfin-1 mRNA, and the high degree of microRNA-binding site evolutionary conservation indicates that all members of the Drosophila genus employ a similar strategy to regulate the onset and extinction dynamics of Nerfin-1 expression.

  6. Narrowing the gap between eye care needs and service provision: a model to dynamically regulate the flow of personnel through a multiple entry and exit training programme

    Directory of Open Access Journals (Sweden)

    Masnick Keith

    2009-05-01

    Full Text Available Abstract Background The purpose of this paper is to present a complex yet transparent, computable model to simulate the regulation of the flow of personnel through a previously described multiple-entry, multiple-exit eye care training scheme linked to the health workforce. This methodology should be a useful tool for the planner; it can address changes and feedbacks over time and be sensitive to any unexpected consequences of the interactions. The same model template can be applied to calculate the finances associated with the personnel flow. Presentation of the hypothesis The worth of any model or set of concepts of human resources for health is considerably enhanced by actual field application. However, implementation involves the selection of one set of parameters and a large, long-term commitment of resources. A far less expensive and time-consuming, yet still effective, method of testing assumptions and ideas would be to simulate their application using a variety of possible inputs, structural configurations and/or desired outcomes. To that end, this paper presents a computable, dynamic model of personnel flows within a health system. Testing the hypothesis Some testing of the model has been demonstrated in a previous paper. However, the value of the model is that all stakeholders can enter their own data and parameter assumptions and readily review the outcomes. Implications of the hypothesis The complex yet easy-to-use model presented in this paper opens the debate on current and future policy to any stakeholder. A very wide range of scenarios can be considered and a selected option can be monitored and changed dynamically over time.

  7. Analysis of dynamic multiplicity fluctuations at PHOBOS

    Science.gov (United States)

    Chai, Zhengwei; PHOBOS Collaboration; Back, B. B.; Baker, M. D.; Ballintijn, M.; Barton, D. S.; Betts, R. R.; Bickley, A. A.; Bindel, R.; Budzanowski, A.; Busza, W.; Carroll, A.; Chai, Z.; Decowski, M. P.; García, E.; George, N.; Gulbrandsen, K.; Gushue, S.; Halliwell, C.; Hamblen, J.; Heintzelman, G. A.; Henderson, C.; Hofman, D. J.; Hollis, R. S.; Holynski, R.; Holzman, B.; Iordanova, A.; Johnson, E.; Kane, J. L.; Katzy, J.; Khan, N.; Kucewicz, W.; Kulinich, P.; Kuo, C. M.; Lin, W. T.; Manly, S.; McLeod, D.; Mignerey, A. C.; Nouicer, R.; Olszewski, A.; Pak, R.; Park, I. C.; Pernegger, H.; Reed, C.; Remsberg, L. P.; Reuter, M.; Roland, C.; Roland, G.; Rosenberg, L.; Sagerer, J.; Sarin, P.; Sawicki, P.; Skulski, W.; Steinberg, P.; Stephans, G. S. F.; Sukhanov, A.; Tang, J. L.; Trzupek, A.; Vale, C.; van Nieuwenhuizen, G. J.; Verdier, R.; Wolfs, F. L. H.; Wosiek, B.; Wozniak, K.; Wuosmaa, A. H.; Wyslouch, B.

    2005-01-01

    This paper presents the analysis of the dynamic fluctuations in the inclusive charged particle multiplicity measured by PHOBOS for Au+Au collisions at surdsNN = 200GeV within the pseudo-rapidity range of -3 < η < 3. First the definition of the fluctuations observables used in this analysis is presented, together with the discussion of their physics meaning. Then the procedure for the extraction of dynamic fluctuations is described. Some preliminary results are included to illustrate the correlation features of the fluctuation observable. New dynamic fluctuations results will be available in a later publication.

  8. Dynamic ubiquitin signaling in cell cycle regulation.

    Science.gov (United States)

    Gilberto, Samuel; Peter, Matthias

    2017-08-07

    The cell division cycle is driven by a collection of enzymes that coordinate DNA duplication and separation, ensuring that genomic information is faithfully and perpetually maintained. The activity of the effector proteins that perform and coordinate these biological processes oscillates by regulated expression and/or posttranslational modifications. Ubiquitylation is a cardinal cellular modification and is long known for driving cell cycle transitions. In this review, we emphasize emerging concepts of how ubiquitylation brings the necessary dynamicity and plasticity that underlie the processes of DNA replication and mitosis. New studies, often focusing on the regulation of chromosomal proteins like DNA polymerases or kinetochore kinases, are demonstrating that ubiquitylation is a versatile modification that can be used to fine-tune these cell cycle events, frequently through processes that do not involve proteasomal degradation. Understanding how the increasing variety of identified ubiquitin signals are transduced will allow us to develop a deeper mechanistic perception of how the multiple factors come together to faithfully propagate genomic information. Here, we discuss these and additional conceptual challenges that are currently under study toward understanding how ubiquitin governs cell cycle regulation. © 2017 Gilberto and Peter.

  9. Multiple quantum spin dynamics of entanglement

    International Nuclear Information System (INIS)

    Doronin, Serge I.

    2003-01-01

    The dynamics of entanglement is investigated on the basis of exactly solvable models of multiple quantum (MQ) NMR spin dynamics. It is shown that the time evolution of MQ coherences of systems of coupled nuclear spins in solids is directly connected with dynamics of the quantum entanglement. We studied analytically the dynamics of entangled states for two- and three-spin systems coupled by the dipole-dipole interaction. In this case the dynamics of the quantum entanglement is uniquely determined by the time evolution of MQ coherences of the second order. The real part of the density matrix describing MQ dynamics in solids is responsible for MQ coherences of the zeroth order while its imaginary part is responsible for the second order. Thus, one can conclude that the dynamics of the entanglement is connected with transitions from the real part of the density matrix to the imaginary one, and vice versa. A pure state which generalizes the Greenberger-Horne-Zeilinger (GHZ) and W states is found. Different measures of the entanglement of this state are analyzed for tripartite systems

  10. F429 Regulation of Tunnels in Cytochrome P450 2B4: A Top Down Study of Multiple Molecular Dynamics Simulations.

    Directory of Open Access Journals (Sweden)

    Giordano Mancini

    Full Text Available The root causes of the outcomes of the single-site mutation in enzymes remain by and large not well understood. This is the case of the F429H mutant of the cytochrome P450 (CYP 2B4 enzyme where the substitution, on the proximal surface of the active site, of a conserved phenylalanine 429 residue with histidine seems to hamper the formation of the active species, Compound I (porphyrin cation radical-Fe(IV = O, Cpd I from the ferric hydroperoxo (Fe(IIIOOH-, Cpd 0 precursor. Here we report a study based on extensive molecular dynamic (MD simulations of 4 CYP-2B4 point mutations compared to the WT enzyme, having the goal of better clarifying the importance of the proximal Phe429 residue on CYP 2B4 catalytic properties. To consolidate the huge amount of data coming from five simulations and extract the most distinct structural features of the five species studied we made an extensive use of cluster analysis. The results show that all studied single polymorphisms of F429, with different side chain properties: i drastically alter the reservoir of conformations accessible by the protein, perturbing global dynamics ii expose the thiolate group of residue Cys436 to the solvent, altering the electronic properties of Cpd0 and iii affect the various ingress and egress channels connecting the distal sites with the bulk environment, altering the reversibility of these channels. In particular, it was observed that the wild type enzyme exhibits unique structural features as compared to all mutant species in terms of weak interactions (hydrogen bonds that generate a completely different dynamical behavior of the complete system. Albeit not conclusive, the current computational investigation sheds some light on the subtle and critical effects that proximal single-site mutations can exert on the functional mechanisms of human microsomal CYPs which should go rather far beyond local structure characterization.

  11. Dynamics of multiple-goal pursuit.

    Science.gov (United States)

    Louro, Maria J; Pieters, Rik; Zeelenberg, Marcel

    2007-08-01

    The authors propose and test a model of multiple-goal pursuit that specifies how individuals allocate effort among multiple goals over time. The model predicts that whether individuals decide to step up effort, coast, abandon the current goal, or switch to pursue another goal is determined jointly by the emotions that flow from prior goal progress and the proximity to future goal attainment, and proximally determined by changes in expectancies about goal attainment. Results from a longitudinal diary study and 2 experiments show that positive and negative goal-related emotions can have diametrically opposing effects on goal-directed behavior, depending on the individual's proximity to goal attainment. The findings resolve contrasting predictions about the influence of positive and negative emotions in volitional behavior, critically amend the goal gradient hypothesis, and provide new insights into the dynamics and determinants of multiple-goal pursuit.

  12. Basic dynamics at a multiple resonance

    International Nuclear Information System (INIS)

    Ferraz-Mello, S.; Yokoyama, T.

    The problem of multiple resonance is dealt with as it occurs in Celestial Mechanics and in non-linear Mechanics. In perturbation theory small divisors occur as a consequence of the fact that the flows in the phase space of the real system and the flows in the phase space of the so-called undisturbed system are not homeomorphic at all. Whatever the perturbation technique we adopt, the first step is to correct the topology of the undisturbed flows. It is shown that at a multiple resonance we are led to dynamical systems that are generally non-integrable. The basic representatives of these systems are the n-pendulums theta sup(:) sub(k) = σ sub(j)A sub(jk) sin theta sub(j). Multiple resonances are classified as syndetic or asyndetic following the eigenvalues of a quadratic form. Some degenerate cases are also presented. (Author) [pt

  13. High Dynamic Range Imaging Using Multiple Exposures

    Science.gov (United States)

    Hou, Xinglin; Luo, Haibo; Zhou, Peipei; Zhou, Wei

    2017-06-01

    It is challenging to capture a high-dynamic range (HDR) scene using a low-dynamic range (LDR) camera. This paper presents an approach for improving the dynamic range of cameras by using multiple exposure images of same scene taken under different exposure times. First, the camera response function (CRF) is recovered by solving a high-order polynomial in which only the ratios of the exposures are used. Then, the HDR radiance image is reconstructed by weighted summation of the each radiance maps. After that, a novel local tone mapping (TM) operator is proposed for the display of the HDR radiance image. By solving the high-order polynomial, the CRF can be recovered quickly and easily. Taken the local image feature and characteristic of histogram statics into consideration, the proposed TM operator could preserve the local details efficiently. Experimental result demonstrates the effectiveness of our method. By comparison, the method outperforms other methods in terms of imaging quality.

  14. Minsky and dynamic macroprudential regulation

    Directory of Open Access Journals (Sweden)

    Jan Kregel

    2014-06-01

    Full Text Available In the context of current debates about the proper form of prudential regulation and proposals for the imposition of liquidity and capital ratios, the paper examines Hyman Minsky’s work as a consultant to government agencies exploring financial regulatory reform in the 1960s. As the author explains, this often-overlooked early work, a precursor to Minsky’s “financial instability hypothesis”, serves as yet another useful guide to explaining why regulation and supervision in the lead-up to the 2008 financial crisis were flawed, and why the approach to reregulation after the crisis has been incomplete.

  15. cDREM: inferring dynamic combinatorial gene regulation.

    Science.gov (United States)

    Wise, Aaron; Bar-Joseph, Ziv

    2015-04-01

    Genes are often combinatorially regulated by multiple transcription factors (TFs). Such combinatorial regulation plays an important role in development and facilitates the ability of cells to respond to different stresses. While a number of approaches have utilized sequence and ChIP-based datasets to study combinational regulation, these have often ignored the combinational logic and the dynamics associated with such regulation. Here we present cDREM, a new method for reconstructing dynamic models of combinatorial regulation. cDREM integrates time series gene expression data with (static) protein interaction data. The method is based on a hidden Markov model and utilizes the sparse group Lasso to identify small subsets of combinatorially active TFs, their time of activation, and the logical function they implement. We tested cDREM on yeast and human data sets. Using yeast we show that the predicted combinatorial sets agree with other high throughput genomic datasets and improve upon prior methods developed to infer combinatorial regulation. Applying cDREM to study human response to flu, we were able to identify several combinatorial TF sets, some of which were known to regulate immune response while others represent novel combinations of important TFs.

  16. Dynamic hydro-climatic networks in pristine and regulated rivers

    Science.gov (United States)

    Botter, G.; Basso, S.; Lazzaro, G.; Doulatyari, B.; Biswal, B.; Schirmer, M.; Rinaldo, A.

    2014-12-01

    Flow patterns observed at-a-station are the dynamical byproduct of a cascade of processes involving different compartments of the hydro-climatic network (e.g., climate, rainfall, soil, vegetation) that regulates the transformation of rainfall into streamflows. In complex branching rivers, flow regimes result from the heterogeneous arrangement around the stream network of multiple hydrologic cascades that simultaneously occur within distinct contributing areas. As such, flow regimes are seen as the integrated output of a complex "network of networks", which can be properly characterized by its degree of temporal variability and spatial heterogeneity. Hydrologic networks that generate river flow regimes are dynamic in nature. In pristine rivers, the time-variance naturally emerges at multiple timescales from climate variability (namely, seasonality and inter-annual fluctuations), implying that the magnitude (and the features) of the water flow between two nodes may be highly variable across different seasons and years. Conversely, the spatial distribution of river flow regimes within pristine rivers involves scale-dependent transport features, as well as regional climatic and soil use gradients, which in small and meso-scale catchments (A guarantee quite uniform flow regimes and high spatial correlations. Human-impacted rivers, instead, constitute hybrid networks where observed spatio-temporal patterns are dominated by anthropogenic shifts, such as landscape alterations and river regulation. In regulated rivers, the magnitude and the features of water flows from node to node may change significantly through time due to damming and withdrawals. However, regulation may impact river regimes in a spatially heterogeneous manner (e.g. in localized river reaches), with a significant decrease of spatial correlations and network connectivity. Provided that the spatial and temporal dynamics of flow regimes in complex rivers may strongly impact important biotic processes

  17. Multiple upstream modules regulate zebrafish myf5 expression

    Directory of Open Access Journals (Sweden)

    Weng Chih-Wei

    2007-01-01

    Full Text Available Abstract Background Myf5 is one member of the basic helix-loop-helix family of transcription factors, and it functions as a myogenic factor that is important for the specification and differentiation of muscle cells. The expression of myf5 is somite- and stage-dependent during embryogenesis through a delicate regulation. However, this complex regulatory mechanism of myf5 is not clearly understood. Results We isolated a 156-kb bacterial artificial chromosome clone that includes an upstream 80-kb region and a downstream 70-kb region of zebrafish myf5 and generated a transgenic line carrying this 156-kb segment fused to a green fluorescent protein (GFP reporter gene. We find strong GFP expression in the most rostral somite and in the presomitic mesoderm during segmentation stages, similar to endogenous myf5 expression. Later, the GFP signals persist in caudal somites near the tail bud but are down-regulated in the older, rostral somites. During the pharyngula period, we detect GFP signals in pectoral fin buds, dorsal rostral myotomes, hypaxial myotomes, and inferior oblique and superior oblique muscles, a pattern that also corresponds well with endogenous myf5 transcripts. To characterize the specific upstream cis-elements that regulate this complex and dynamic expression pattern, we also generated several transgenic lines that harbor various lengths within the upstream 80-kb segment. We find that (1 the -80 kb/-9977 segment contains a fin and cranial muscle element and a notochord repressor; (2 the -9977/-6213 segment contains a strong repressive element that does not include the notochord-specific repressor; (3 the -6212/-2938 segment contains tissue-specific elements for bone and spinal cord; (4 the -2937/-291 segment contains an eye enhancer, and the -2937/-2457 segment is required for notochord and myocyte expression; and (5 the -290/-1 segment is responsible for basal transcription in somites and the presomitic mesoderm. Conclusion We suggest

  18. Teacher regulation of multiple computer-supported collaborating groups

    NARCIS (Netherlands)

    Van Leeuwen, Anouschka; Janssen, Jeroen; Erkens, Gijsbert; Brekelmans, Mieke

    2015-01-01

    Teachers regulating groups of students during computer-supported collaborative learning (CSCL) face the challenge of orchestrating their guidance at student, group, and class level. During CSCL, teachers can monitor all student activity and interact with multiple groups at the same time. Not much is

  19. Collective modes in multiband superfluids and superconductors: Multiple dynamical classes

    International Nuclear Information System (INIS)

    Ota, Yukihiro; Machida, Masahiko; Koyama, Tomio; Aoki, Hideo

    2011-01-01

    One important way to characterize the states having a gauge symmetry spontaneously broken over multibands is to look at their collective excitation modes. We find that a three-band system has multiple Leggett modes with significantly different masses, which can be classified into different dynamical classes according to whether multiple interband Josephson currents add or cancel. This provides a way to dynamically characterize multiband superconductivity while the pairing symmetry is a static property.

  20. Optimization of multi-response dynamic systems integrating multiple ...

    African Journals Online (AJOL)

    It also results in better optimization performance than back-propagation neural network-based approach and data mining-based approach reported by the past researchers. Keywords: multiple responses, multiple regression, weighted dynamic signal-to-noise ratio, performance measure modelling, response function ...

  1. Static and dynamic properties of multiple light scattering

    Science.gov (United States)

    Štěpánek, Petr

    1993-11-01

    We have examined the onset and evolution of multiple scattering of light on a series of latex dispersions as a function of increasing volume concentration φ of particles. We have shown that using vertically polarized incident light, the static scattered intensity becomes progressively depolarized, with increasing φ. The polarization of scattered light is completely random in the limit of strong multiple scattering. The spectra of decay times of dynamic light scattering display a region of oligo scattering at intermediate φ where both the single and multiple scattering components can be dynamically identified. For φ≳0.03 the limit of diffusive transport of light is attained. The obtained results confirm that our earlier measurements of dynamic light scattering on systems exhibiting critical opalescence are not influenced by multiple light scattering.

  2. Image Alignment for Multiple Camera High Dynamic Range Microscopy

    OpenAIRE

    Eastwood, Brian S.; Childs, Elisabeth C.

    2012-01-01

    This paper investigates the problem of image alignment for multiple camera high dynamic range (HDR) imaging. HDR imaging combines information from images taken with different exposure settings. Combining information from multiple cameras requires an alignment process that is robust to the intensity differences in the images. HDR applications that use a limited number of component images require an alignment technique that is robust to large exposure differences. We evaluate the suitability fo...

  3. AMBIDEXTER Dynamics and Self-Regulation Capability

    International Nuclear Information System (INIS)

    Oh, Se Kee; Lee, Young Joon; Ham, Tae Kyu; Seo, Myung Hwan; Hong, Sung Taek; Kwon, Tae An

    2009-01-01

    Safety-related events in a nuclear reactor system are mostly incurred by sudden imbalance between their heat source and sink behaviors. Controllability and resiliency are assessed if the system be safely recoverable from the imbalance. Inherent safety characteristics of the reactor should be an ideal design philosophy in this aspect. The AMBIDEXTER safety design was explored with maximum reliance on counteractive responses by the system itself. As for the realization, negative reactivity feedback and fail-safe criteria are the fundamental considerations. Details of how to implement them in the design can be found in the paper accompanied. the reactor and the primary heat exchanger are integrated into a closed loop in the vessel. The fuel salt flows downwardly in the outer core region, gains fission heat and then, rises upwardly through the central inner core region where resonance absorbers face better conversion chance. In the primary heat exchanger, heat transfer between the tube-side fuel salt and the shell-side coolant salt is made. For chemical processing, part of the fuel salt flow is discharged from the heat exchanger and returns to the reactor through bypass line. This paper examines the dynamic performances of the AMBIDEXTER reactor system to investigate the range of its self-regulation capability and safety impacts

  4. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

    Science.gov (United States)

    Andlauer, Till F M; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A; Loleit, Verena; Luessi, Felix; Meuth, Sven G; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

    2016-06-01

    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.

  5. Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics

    Science.gov (United States)

    Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen; Christensen, Sune M.; Abel, Steven M.; Iwig, Jeff; Wu, Hung-Jen; Gureasko, Jodi; Rhodes, Christopher; Petit, Rebecca S.; Hansen, Scott D.; Thill, Peter; Yu, Cheng-Han; Stamou, Dimitrios; Chakraborty, Arup K.; Kuriyan, John; Groves, Jay T.

    2014-01-01

    Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras–guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average. PMID:24994643

  6. Myosin II dynamics are regulated by tension in intercalating cells.

    Science.gov (United States)

    Fernandez-Gonzalez, Rodrigo; Simoes, Sérgio de Matos; Röper, Jens-Christian; Eaton, Suzanne; Zallen, Jennifer A

    2009-11-01

    Axis elongation in Drosophila occurs through polarized cell rearrangements driven by actomyosin contractility. Myosin II promotes neighbor exchange through the contraction of single cell boundaries, while the contraction of myosin II structures spanning multiple pairs of cells leads to rosette formation. Here we show that multicellular actomyosin cables form at a higher frequency than expected by chance, indicating that cable assembly is an active process. Multicellular cables are sites of increased mechanical tension as measured by laser ablation. Fluorescence recovery after photobleaching experiments show that myosin II is stabilized at the cortex in regions of increased tension. Myosin II is recruited in response to an ectopic force and relieving tension leads to a rapid loss of myosin, indicating that tension is necessary and sufficient for cortical myosin localization. These results demonstrate that myosin II dynamics are regulated by tension in a positive feedback loop that leads to multicellular actomyosin cable formation and efficient tissue elongation.

  7. Multiple roles for the actin cytoskeleton during regulated exocytosis

    Science.gov (United States)

    Porat-Shliom, Natalie; Milberg, Oleg; Masedunskas, Andrius; Weigert, Roberto

    2014-01-01

    Regulated exocytosis is the main mechanism utilized by specialized secretory cells to deliver molecules to the cell surface by virtue of membranous containers (i.e. secretory vesicles). The process involves a series of highly coordinated and sequential steps, which include the biogenesis of the vesicles, their delivery to the cell periphery, their fusion with the plasma membrane and the release of their content into the extracellular space. Each of these steps is regulated by the actin cytoskeleton. In this review, we summarize the current knowledge regarding the involvement of actin and its associated molecules during each of the exocytic steps in vertebrates, and suggest that the overall role of the actin cytoskeleton during regulated exocytosis is linked to the architecture and the physiology of the secretory cells under examination. Specifically, in neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small secretory vesicles that undergo rapid exocytosis (on the order of milliseconds), the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily as a functional barrier and facilitates docking. In exocrine and other secretory cells, which contain large secretory vesicles that undergo slow exocytosis (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events, where it regulates the dynamics of the fusion pore, facilitates the integration of the vesicles into the plasma membrane, provides structural support, and promotes the expulsion of large cargo molecules. PMID:22986507

  8. Modelling and Analysis of a New Piezoelectric Dynamic Balance Regulator

    Directory of Open Access Journals (Sweden)

    Mu-Xun Xu

    2012-11-01

    Full Text Available In this paper, a new piezoelectric dynamic balance regulator, which can be used in motorised spindle systems, is presented. The dynamic balancing adjustment mechanism is driven by an in-plane bending vibration from an annular piezoelectric stator excited by a high-frequency sinusoidal input voltage. This device has different construction, characteristics and operating principles than a conventional balance regulator. In this work, a dynamic model of the regulator is first developed using a detailed analytical method. Thereafter, MATLAB is employed to numerically simulate the relations between the dominant parameters and the characteristics of the regulator based on thedynamic model. Finally, experimental measurements are used to certify the validity of the dynamic model. Consequently, the mathematical model presented and analysed in this paper can be used as a tool for optimising the design of a piezoelectric dynamic balance regulator during steady state operation.

  9. Criteria for stability of linear dynamical systems with multiple delays ...

    African Journals Online (AJOL)

    In this study we considered a linear Dynamical system with multiple delays and find suitable conditions on the systems parameters such that for a given initial function, we can define a mapping in a carefully chosen complete metric space on which the mapping has a unique fixed point. An asymptotic stability theory for the ...

  10. Dynamic Initiation and Propagation of Multiple Cracks in Brittle Materials

    Directory of Open Access Journals (Sweden)

    Xiaodan Ren

    2013-07-01

    Full Text Available Brittle materials such as rock and ceramic usually exhibit apparent increases of strength and toughness when subjected to dynamic loading. The reasons for this phenomenon are not yet well understood, although a number of hypotheses have been proposed. Based on dynamic fracture mechanics, the present work offers an alternate insight into the dynamic behaviors of brittle materials. Firstly, a single crack subjected to stress wave excitations is investigated to obtain the dynamic crack-tip stress field and the dynamic stress intensity factor. Second, based on the analysis of dynamic stress intensity factor, the fracture initiation sizes and crack size distribution under different loading rates are obtained, and the power law with the exponent of −2/3 is derived to describe the fracture initiation size. Third, with the help of the energy balance concept, the dynamic increase of material strength is directly derived based on the proposed multiple crack evolving criterion. Finally, the model prediction is compared with the dynamic impact experiments, and the model results agree well with the experimentally measured dynamic increasing factor (DIF.

  11. Dynamic Characteristics Analysis and Stabilization of PV-Based Multiple Microgrid Clusters

    DEFF Research Database (Denmark)

    Zhao, Zhuoli; Yang, Ping; Wang, Yuewu

    2018-01-01

    -based multiple microgrid clusters. A detailed small-signal model for PV-based microgrid clusters considering local adaptive dynamic droop control mechanism of the voltage-source PV system is developed. The complete dynamic model is then used to access and compare the dynamic characteristics of the single...... microgrid and interconnected microgrids. In order to enhance system stability of the PV microgrid clusters, a tie-line flow and stabilization strategy is proposed to suppress the introduced interarea and local oscillations. Robustly selecting of the key control parameters is transformed to a multiobjective......As the penetration of PV generation increases, there is a growing operational demand on PV systems to participate in microgrid frequency regulation. It is expected that future distribution systems will consist of multiple microgrid clusters. However, interconnecting PV microgrids may lead to system...

  12. Multiple time step integrators in ab initio molecular dynamics

    International Nuclear Information System (INIS)

    Luehr, Nathan; Martínez, Todd J.; Markland, Thomas E.

    2014-01-01

    Multiple time-scale algorithms exploit the natural separation of time-scales in chemical systems to greatly accelerate the efficiency of molecular dynamics simulations. Although the utility of these methods in systems where the interactions are described by empirical potentials is now well established, their application to ab initio molecular dynamics calculations has been limited by difficulties associated with splitting the ab initio potential into fast and slowly varying components. Here we present two schemes that enable efficient time-scale separation in ab initio calculations: one based on fragment decomposition and the other on range separation of the Coulomb operator in the electronic Hamiltonian. We demonstrate for both water clusters and a solvated hydroxide ion that multiple time-scale molecular dynamics allows for outer time steps of 2.5 fs, which are as large as those obtained when such schemes are applied to empirical potentials, while still allowing for bonds to be broken and reformed throughout the dynamics. This permits computational speedups of up to 4.4x, compared to standard Born-Oppenheimer ab initio molecular dynamics with a 0.5 fs time step, while maintaining the same energy conservation and accuracy

  13. Neural Computations in a Dynamical System with Multiple Time Scales

    Directory of Open Access Journals (Sweden)

    Yuanyuan Mi

    2016-09-01

    Full Text Available Neural systems display rich short-term dynamics at various levels, e.g., spike-frequencyadaptation (SFA at single neurons, and short-term facilitation (STF and depression (STDat neuronal synapses. These dynamical features typically covers a broad range of time scalesand exhibit large diversity in different brain regions. It remains unclear what the computationalbenefit for the brain to have such variability in short-term dynamics is. In this study, we proposethat the brain can exploit such dynamical features to implement multiple seemingly contradictorycomputations in a single neural circuit. To demonstrate this idea, we use continuous attractorneural network (CANN as a working model and include STF, SFA and STD with increasing timeconstants in their dynamics. Three computational tasks are considered, which are persistent activity,adaptation, and anticipative tracking. These tasks require conflicting neural mechanisms, andhence cannot be implemented by a single dynamical feature or any combination with similar timeconstants. However, with properly coordinated STF, SFA and STD, we show that the network isable to implement the three computational tasks concurrently. We hope this study will shed lighton the understanding of how the brain orchestrates its rich dynamics at various levels to realizediverse cognitive functions.

  14. Neural Computations in a Dynamical System with Multiple Time Scales.

    Science.gov (United States)

    Mi, Yuanyuan; Lin, Xiaohan; Wu, Si

    2016-01-01

    Neural systems display rich short-term dynamics at various levels, e.g., spike-frequency adaptation (SFA) at the single-neuron level, and short-term facilitation (STF) and depression (STD) at the synapse level. These dynamical features typically cover a broad range of time scales and exhibit large diversity in different brain regions. It remains unclear what is the computational benefit for the brain to have such variability in short-term dynamics. In this study, we propose that the brain can exploit such dynamical features to implement multiple seemingly contradictory computations in a single neural circuit. To demonstrate this idea, we use continuous attractor neural network (CANN) as a working model and include STF, SFA and STD with increasing time constants in its dynamics. Three computational tasks are considered, which are persistent activity, adaptation, and anticipative tracking. These tasks require conflicting neural mechanisms, and hence cannot be implemented by a single dynamical feature or any combination with similar time constants. However, with properly coordinated STF, SFA and STD, we show that the network is able to implement the three computational tasks concurrently. We hope this study will shed light on the understanding of how the brain orchestrates its rich dynamics at various levels to realize diverse cognitive functions.

  15. Computer studies of multiple-quantum spin dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Murdoch, J.B.

    1982-11-01

    The excitation and detection of multiple-quantum (MQ) transitions in Fourier transform NMR spectroscopy is an interesting problem in the quantum mechanical dynamics of spin systems as well as an important new technique for investigation of molecular structure. In particular, multiple-quantum spectroscopy can be used to simplify overly complex spectra or to separate the various interactions between a nucleus and its environment. The emphasis of this work is on computer simulation of spin-system evolution to better relate theory and experiment.

  16. Computer studies of multiple-quantum spin dynamics

    International Nuclear Information System (INIS)

    Murdoch, J.B.

    1982-11-01

    The excitation and detection of multiple-quantum (MQ) transitions in Fourier transform NMR spectroscopy is an interesting problem in the quantum mechanical dynamics of spin systems as well as an important new technique for investigation of molecular structure. In particular, multiple-quantum spectroscopy can be used to simplify overly complex spectra or to separate the various interactions between a nucleus and its environment. The emphasis of this work is on computer simulation of spin-system evolution to better relate theory and experiment

  17. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

    Science.gov (United States)

    Andlauer, Till F. M.; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A.; Loleit, Verena; Luessi, Felix; Meuth, Sven G.; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H.; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K.; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O.; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B.; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M.; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M.; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

    2016-01-01

    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis. PMID:27386562

  18. Image Alignment for Multiple Camera High Dynamic Range Microscopy.

    Science.gov (United States)

    Eastwood, Brian S; Childs, Elisabeth C

    2012-01-09

    This paper investigates the problem of image alignment for multiple camera high dynamic range (HDR) imaging. HDR imaging combines information from images taken with different exposure settings. Combining information from multiple cameras requires an alignment process that is robust to the intensity differences in the images. HDR applications that use a limited number of component images require an alignment technique that is robust to large exposure differences. We evaluate the suitability for HDR alignment of three exposure-robust techniques. We conclude that image alignment based on matching feature descriptors extracted from radiant power images from calibrated cameras yields the most accurate and robust solution. We demonstrate the use of this alignment technique in a high dynamic range video microscope that enables live specimen imaging with a greater level of detail than can be captured with a single camera.

  19. Joint Dynamic Pricing of Multiple Perishable Products Under Consumer Choice

    OpenAIRE

    Yalç{\\i}n Akçay; Harihara Prasad Natarajan; Susan H. Xu

    2010-01-01

    In response to competitive pressures, firms are increasingly adopting revenue management opportunities afforded by advances in information and communication technologies. Motivated by these revenue management initiatives in industry, we consider a dynamic pricing problem facing a firm that sells given initial inventories of multiple substitutable and perishable products over a finite selling horizon. Because the products are substitutable, individual product demands are linked through consume...

  20. Stochastic dynamics of a delayed bistable system with multiplicative noise

    Energy Technology Data Exchange (ETDEWEB)

    Dung, Nguyen Tien, E-mail: dung-nguyentien10@yahoo.com, E-mail: dungnt@fpt.edu.vn [Department of Mathematics, FPT University, No 8 Ton That Thuyet, My Dinh, Tu Liem, Hanoi (Viet Nam)

    2014-05-15

    In this paper we investigate the properties of a delayed bistable system under the effect of multiplicative noise. We first prove the existence and uniqueness of the positive solution and show that its moments are uniformly bounded. Then, we study stochastic dynamics of the solution in long time, the lower and upper bounds for the paths and an estimate for the average value are provided.

  1. SACHET, Dynamic Fission Products Inventory in PWR Multiple Compartment System

    International Nuclear Information System (INIS)

    Kodaira, Hideki

    1990-01-01

    1 - Description of program or function: SACHET evaluates the dynamic fission product inventories in the multiple compartment system of pressurized water reactor (PWR) plants. 2 - Method of solution: SACHET utilizes a matrix of fission product core inventory which is previously calculated by the ORIGEN code. 3 - Restrictions on the complexity of the problem: Liquid wastes such as chemical waste and detergent waste are not included

  2. Experimentation of Eigenvector Dynamics in a Multiple Input Multiple Output Channel in the 5GHz Band

    DEFF Research Database (Denmark)

    Brown, Tim; Eggers, Patrick Claus F.; Katz, Marcos

    2005-01-01

    Much research has been carried out on the production of both physical and non physical Multiple Input Multiple Output channel models with regard to increased channel capacity as well as analysis of eigenvalues through the use of singular value decomposition. Little attention has been paid...... to the analysis of vector dynamics in terms of how the state of eigenvectors will change as a mobile is moving through a changing physical environment. This is important in terms of being able to track the orthogonal eigenmodes at system level, while also relieving the burden of tracking of the full channel...

  3. Dynamical Analysis of bantam-Regulated Drosophila Circadian Rhythm Model

    Science.gov (United States)

    Li, Ying; Liu, Zengrong

    MicroRNAs (miRNAs) interact with 3‧untranslated region (UTR) elements of target genes to regulate mRNA stability or translation, and play a crucial role in regulating many different biological processes. bantam, a conserved miRNA, is involved in several functions, such as regulating Drosophila growth and circadian rhythm. Recently, it has been discovered that bantam plays a crucial role in the core circadian pacemaker. In this paper, based on experimental observations, a detailed dynamical model of bantam-regulated circadian clock system is developed to show the post-transcriptional behaviors in the modulation of Drosophila circadian rhythm, in which the regulation of bantam is incorporated into a classical model. The dynamical behaviors of the model are consistent with the experimental observations, which shows that bantam is an important regulator of Drosophila circadian rhythm. The sensitivity analysis of parameters demonstrates that with the regulation of bantam the system is more sensitive to perturbations, indicating that bantam regulation makes it easier for the organism to modulate its period against the environmental perturbations. The effectiveness in rescuing locomotor activity rhythms of mutated flies shows that bantam is necessary for strong and sustained rhythms. In addition, the biological mechanisms of bantam regulation are analyzed, which may help us more clearly understand Drosophila circadian rhythm regulated by other miRNAs.

  4. Interaction dynamics of multiple mobile robots with simple navigation strategies

    Science.gov (United States)

    Wang, P. K. C.

    1989-01-01

    The global dynamic behavior of multiple interacting autonomous mobile robots with simple navigation strategies is studied. Here, the effective spatial domain of each robot is taken to be a closed ball about its mass center. It is assumed that each robot has a specified cone of visibility such that interaction with other robots takes place only when they enter its visibility cone. Based on a particle model for the robots, various simple homing and collision-avoidance navigation strategies are derived. Then, an analysis of the dynamical behavior of the interacting robots in unbounded spatial domains is made. The article concludes with the results of computer simulations studies of two or more interacting robots.

  5. Bmp indicator mice reveal dynamic regulation of transcriptional response.

    Directory of Open Access Journals (Sweden)

    Anna L Javier

    Full Text Available Cellular responses to Bmp ligands are regulated at multiple levels, both extracellularly and intracellularly. Therefore, the presence of these growth factors is not an accurate indicator of Bmp signaling activity. While a common approach to detect Bmp signaling activity is to determine the presence of phosphorylated forms of Smad1, 5 and 8 by immunostaining, this approach is time consuming and not quantitative. In order to provide a simpler readout system to examine the presence of Bmp signaling in developing animals, we developed BRE-gal mouse embryonic stem cells and a transgenic mouse line that specifically respond to Bmp ligand stimulation. Our reporter identifies specific transcriptional responses that are mediated by Smad1 and Smad4 with the Schnurri transcription factor complex binding to a conserved Bmp-Responsive Element (BRE, originally identified among Drosophila, Xenopus and human Bmp targets. Our BRE-gal mES cells specifically respond to Bmp ligands at concentrations as low as 5 ng/ml; and BRE-gal reporter mice, derived from the BRE-gal mES cells, show dynamic activity in many cellular sites, including extraembryonic structures and mammary glands, thereby making this a useful scientific tool.

  6. The dynamic landscape of gene regulation during Bombyx mori oogenesis.

    Science.gov (United States)

    Zhang, Qiang; Sun, Wei; Sun, Bang-Yong; Xiao, Yang; Zhang, Ze

    2017-09-11

    Oogenesis in the domestic silkworm (Bombyx mori) is a complex process involving previtellogenesis, vitellogenesis and choriogenesis. During this process, follicles show drastic morphological and physiological changes. However, the genome-wide regulatory profiles of gene expression during oogenesis remain to be determined. In this study, we obtained time-series transcriptome data and used these data to reveal the dynamic landscape of gene regulation during oogenesis. A total of 1932 genes were identified to be differentially expressed among different stages, most of which occurred during the transition from late vitellogenesis to early choriogenesis. Using weighted gene co-expression network analysis, we identified six stage-specific gene modules that correspond to multiple regulatory pathways. Strikingly, the biosynthesis pathway of the molting hormone 20-hydroxyecdysone (20E) was enriched in one of the modules. Further analysis showed that the ecdysteroid 20-hydroxylase gene (CYP314A1) of steroidgenesis genes was mainly expressed in previtellogenesis and early vitellogenesis. However, the 20E-inactivated genes, particularly the ecdysteroid 26-hydroxylase encoding gene (Cyp18a1), were highly expressed in late vitellogenesis. These distinct expression patterns between 20E synthesis and catabolism-related genes might ensure the rapid decline of the hormone titer at the transition point from vitellogenesis to choriogenesis. In addition, we compared landscapes of gene regulation between silkworm (Lepidoptera) and fruit fly (Diptera) oogeneses. Our results show that there is some consensus in the modules of gene co-expression during oogenesis in these insects. The data presented in this study provide new insights into the regulatory mechanisms underlying oogenesis in insects with polytrophic meroistic ovaries. The results also provide clues for further investigating the roles of epigenetic reconfiguration and circadian rhythm in insect oogenesis.

  7. Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms

    DEFF Research Database (Denmark)

    Nestoras, Konstantinos; Mohammed, Asma Hadi; Schreurs, Ann-Sofie

    2010-01-01

    The correct levels of deoxyribonucleotide triphosphates and their relative abundance are important to maintain genomic integrity. Ribonucleotide reductase (RNR) regulation is complex and multifaceted. RNR is regulated allosterically by two nucleotide-binding sites, by transcriptional control, and...

  8. Ab initio multiple cloning algorithm for quantum nonadiabatic molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Makhov, Dmitry V.; Shalashilin, Dmitrii V. [Department of Chemistry, University of Leeds, Leeds LS2 9JT (United Kingdom); Glover, William J.; Martinez, Todd J. [Department of Chemistry and The PULSE Institute, Stanford University, Stanford, California 94305, USA and SLAC National Accelerator Laboratory, Menlo Park, California 94025 (United States)

    2014-08-07

    We present a new algorithm for ab initio quantum nonadiabatic molecular dynamics that combines the best features of ab initio Multiple Spawning (AIMS) and Multiconfigurational Ehrenfest (MCE) methods. In this new method, ab initio multiple cloning (AIMC), the individual trajectory basis functions (TBFs) follow Ehrenfest equations of motion (as in MCE). However, the basis set is expanded (as in AIMS) when these TBFs become sufficiently mixed, preventing prolonged evolution on an averaged potential energy surface. We refer to the expansion of the basis set as “cloning,” in analogy to the “spawning” procedure in AIMS. This synthesis of AIMS and MCE allows us to leverage the benefits of mean-field evolution during periods of strong nonadiabatic coupling while simultaneously avoiding mean-field artifacts in Ehrenfest dynamics. We explore the use of time-displaced basis sets, “trains,” as a means of expanding the basis set for little cost. We also introduce a new bra-ket averaged Taylor expansion (BAT) to approximate the necessary potential energy and nonadiabatic coupling matrix elements. The BAT approximation avoids the necessity of computing electronic structure information at intermediate points between TBFs, as is usually done in saddle-point approximations used in AIMS. The efficiency of AIMC is demonstrated on the nonradiative decay of the first excited state of ethylene. The AIMC method has been implemented within the AIMS-MOLPRO package, which was extended to include Ehrenfest basis functions.

  9. Dynamic response of multiple nanobeam system under a moving nanoparticle

    Directory of Open Access Journals (Sweden)

    Shahrokh Hosseini Hashemi

    2018-03-01

    Full Text Available In this article, nonlocal continuum based model of multiple nanobeam system (MNBS under a moving nanoparticle is investigated using Eringen’s nonlocal theory. Beam layers are assumed to be coupled by winkler elastic medium and the nonlocal Euler-Bernoulli beam theory is used to model each layer of beam. The Hamilton’s principle, Eigen function technique and the Laplace transform method are employed to solve the governing equations. Analytical solutions of the transverse displacements for MNBs with simply supported boundary condition are presented for double layered and three layered MNBSs. For higher number of layers, the governing set of equations is solved numerically and the results are presented. This study shows that small-scale parameter has a significant effect on dynamic response of MNBS under a moving nanoparticle. Sensitivity of dynamical deflection to variation of nonlocal parameter, stiffness of Winkler elastic medium and number of nanobeams are presented in nondimensional form for each layer. Keywords: Dynamic response, Analytical solution, Moving particle, Nanobeam, Multi-layered nanobeam

  10. Dynamical simulation of structural multiplicity in grain boundaries

    International Nuclear Information System (INIS)

    Majid, I.; Bristowe, P.D.

    1987-06-01

    Work on a computer simulation study of a low-energy high-angle boundary structure which is not periodic have been recently reported. This result is of interest since grain boundary structures are usually assumed to have a periodicity corresponding to the appropriate coincidence site lattice (CSL) and many experimental observations of the structure of grain boundaries performed using conventional and high-resolution electron microscopy, electron diffraction and x-ray diffraction appear to support this work. However, this work, using empirical interatomic pair potentials and the relaxation method of molecular statics, have simulated a Σ = 5 36.87 0 (001) twist boundary and found a low energy structure having a larger repeat cell than the CSL and is composed of two different types of structural unit that are randomly distributed in the boundary plane. This result, which has been termed the multiplicity of grain boundary structures, has also been found in the simulation of tilt boundaries. The multiplicity phenomenon is of special interest in twist boundaries since it is used as a structural model to explain the x-ray scattering from a Σ = 5 boundary in gold. These scattering patterns had previously remained unexplained using stable structures that had simple CSL periodicity. Also, the effect of having a multiple number of low energy structural units coexisting in the grain boundary is of more general interest since it implies that the boundary structures may be quasi-periodic and, in some circumstances, may even result in a roughening of the boundary plane. This paper extends this work by showing, using molecular dynamics, that a multiplicity of structural units can actually nucleate spontaneously in a high-angle grain boundary at finite temperatures

  11. Dynamic coordinated control laws in multiple agent models

    International Nuclear Information System (INIS)

    Morgan, David S.; Schwartz, Ira B.

    2005-01-01

    We present an active control scheme of a kinetic model of swarming. It has been shown previously that the global control scheme for the model, presented in [Systems Control Lett. 52 (2004) 25], gives rise to spontaneous collective organization of agents into a unified coherent swarm, via steering controls and utilizing long-range attractive and short-range repulsive interactions. We extend these results by presenting control laws whereby a single swarm is broken into independently functioning subswarm clusters. The transition between one coordinated swarm and multiple clustered subswarms is managed simply with a homotopy parameter. Additionally, we present as an alternate formulation, a local control law for the same model, which implements dynamic barrier avoidance behavior, and in which swarm coherence emerges spontaneously

  12. Mapping the structural and dynamical features of multiple p53 DNA binding domains: insights into loop 1 intrinsic dynamics.

    Directory of Open Access Journals (Sweden)

    Suryani Lukman

    Full Text Available The transcription factor p53 regulates cellular integrity in response to stress. p53 is mutated in more than half of cancerous cells, with a majority of the mutations localized to the DNA binding domain (DBD. In order to map the structural and dynamical features of the DBD, we carried out multiple copy molecular dynamics simulations (totaling 0.8 μs. Simulations show the loop 1 to be the most dynamic element among the DNA-contacting loops (loops 1-3. Loop 1 occupies two major conformational states: extended and recessed; the former but not the latter displays correlations in atomic fluctuations with those of loop 2 (~24 Å apart. Since loop 1 binds to the major groove whereas loop 2 binds to the minor groove of DNA, our results begin to provide some insight into the possible mechanism underpinning the cooperative nature of DBD binding to DNA. We propose (1 a novel mechanism underlying the dynamics of loop 1 and the possible tread-milling of p53 on DNA and (2 possible mutations on loop 1 residues to restore the transcriptional activity of an oncogenic mutation at a distant site.

  13. Within-Family Dynamics and Self-Regulation in Preschoolers

    NARCIS (Netherlands)

    Karreman, A.

    2006-01-01

    Separate research lines have stressed the importance of within-family dynamics on the one hand and self-regulation on the other hand for the development and stability of problem behavior in young children. Few empirical studies have directly addressed the relation between family processes and

  14. Stakeholder cooperation: regulating a uranium mine with multiple statutory approvals

    International Nuclear Information System (INIS)

    Bush, M.

    2010-01-01

    Ranger Uranium Mine operates under an Authorisation issued by the Northern Territory Government. In addition, the site is regulated by a set of Environmental Requirements attached to the uranium export permit issued by the Australian Government Department of Resources, Energy and Tourism. A Heap Leach facility proposed for the site could result in a third approval being issued, in accordance with the Environmental Protection and Biodiversity Conservation Act 1999 (EPBC Act). Finding the correct balance to regulate the mine in light of these approvals will be a challenge for the range of stakeholders involved in regulation and oversight of this operation. (author)

  15. Monitoring urban greenness dynamics using multiple endmember spectral mixture analysis.

    Directory of Open Access Journals (Sweden)

    Muye Gan

    Full Text Available Urban greenness is increasingly recognized as an essential constituent of the urban environment and can provide a range of services and enhance residents' quality of life. Understanding the pattern of urban greenness and exploring its spatiotemporal dynamics would contribute valuable information for urban planning. In this paper, we investigated the pattern of urban greenness in Hangzhou, China, over the past two decades using time series Landsat-5 TM data obtained in 1990, 2002, and 2010. Multiple endmember spectral mixture analysis was used to derive vegetation cover fractions at the subpixel level. An RGB-vegetation fraction model, change intensity analysis and the concentric technique were integrated to reveal the detailed, spatial characteristics and the overall pattern of change in the vegetation cover fraction. Our results demonstrated the ability of multiple endmember spectral mixture analysis to accurately model the vegetation cover fraction in pixels despite the complex spectral confusion of different land cover types. The integration of multiple techniques revealed various changing patterns in urban greenness in this region. The overall vegetation cover has exhibited a drastic decrease over the past two decades, while no significant change occurred in the scenic spots that were studied. Meanwhile, a remarkable recovery of greenness was observed in the existing urban area. The increasing coverage of small green patches has played a vital role in the recovery of urban greenness. These changing patterns were more obvious during the period from 2002 to 2010 than from 1990 to 2002, and they revealed the combined effects of rapid urbanization and greening policies. This work demonstrates the usefulness of time series of vegetation cover fractions for conducting accurate and in-depth studies of the long-term trajectories of urban greenness to obtain meaningful information for sustainable urban development.

  16. Dynamic multiple thresholding breast boundary detection algorithm for mammograms

    International Nuclear Information System (INIS)

    Wu, Yi-Ta; Zhou Chuan; Chan, Heang-Ping; Paramagul, Chintana; Hadjiiski, Lubomir M.; Daly, Caroline Plowden; Douglas, Julie A.; Zhang Yiheng; Sahiner, Berkman; Shi Jiazheng; Wei Jun

    2010-01-01

    Purpose: Automated detection of breast boundary is one of the fundamental steps for computer-aided analysis of mammograms. In this study, the authors developed a new dynamic multiple thresholding based breast boundary (MTBB) detection method for digitized mammograms. Methods: A large data set of 716 screen-film mammograms (442 CC view and 274 MLO view) obtained from consecutive cases of an Institutional Review Board approved project were used. An experienced breast radiologist manually traced the breast boundary on each digitized image using a graphical interface to provide a reference standard. The initial breast boundary (MTBB-Initial) was obtained by dynamically adapting the threshold to the gray level range in local regions of the breast periphery. The initial breast boundary was then refined by using gradient information from horizontal and vertical Sobel filtering to obtain the final breast boundary (MTBB-Final). The accuracy of the breast boundary detection algorithm was evaluated by comparison with the reference standard using three performance metrics: The Hausdorff distance (HDist), the average minimum Euclidean distance (AMinDist), and the area overlap measure (AOM). Results: In comparison with the authors' previously developed gradient-based breast boundary (GBB) algorithm, it was found that 68%, 85%, and 94% of images had HDist errors less than 6 pixels (4.8 mm) for GBB, MTBB-Initial, and MTBB-Final, respectively. 89%, 90%, and 96% of images had AMinDist errors less than 1.5 pixels (1.2 mm) for GBB, MTBB-Initial, and MTBB-Final, respectively. 96%, 98%, and 99% of images had AOM values larger than 0.9 for GBB, MTBB-Initial, and MTBB-Final, respectively. The improvement by the MTBB-Final method was statistically significant for all the evaluation measures by the Wilcoxon signed rank test (p<0.0001). Conclusions: The MTBB approach that combined dynamic multiple thresholding and gradient information provided better performance than the breast boundary

  17. Oscillatory Dynamics of the Extracellular Signal-regulated Kinase Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Shankaran, Harish; Wiley, H. S.

    2010-12-01

    The extracellular signal-regulated kinase (ERK) pathway is a central signaling pathway in development and disease and is regulated by multiple negative and positive feedback loops. Recent studies have shown negative feedback from ERK to upstream regulators can give rise to biochemical oscillations with a periodicity of between 15-30 minutes. Feedback due to the stimulated transcription of negative regulators of the ERK pathway can also give rise to transcriptional oscillations with a periodicity of 1-2h. The biological significance of these oscillations is not clear, but recent evidence suggests that transcriptional oscillations participate in developmental processes, such as somite formation. Biochemical oscillations are more enigmatic, but could provide a mechanism for encoding different types of inputs into a common signaling pathway.

  18. Self-regulated dynamical criticality in human ECoG

    Directory of Open Access Journals (Sweden)

    Guillermo eSolovey

    2012-07-01

    Full Text Available Mounting experimental and theoretical results indicate that neural systems are poised near a critical state. In human subjects, however, most evidence comes from functional MRI studies, an indirect measurement of neuronal activity with poor temporal resolution. Electrocorticography (ECoG provides a unique window into human brain activity: each electrode records, with high temporal resolution, the activity resulting from the sum of the local field potentials of sim 10^5 neurons. We show that the human brain ECoG recordings display features of self-regulated dynamical criticality: dynamical modes of activation drift around the critical stability threshold, moving in and out of the unstable region and equilibrating the global dynamical state at a very fast time scale. Moreover, the analysis also reveals differences between the resting state and a motor task, associated with increased stability of a fraction of the dynamical modes.

  19. miR-181a regulates multiple pathways in hypopharyngeal ...

    African Journals Online (AJOL)

    Expression of four pathway reporters were significantly increased (p53/DNA damage, TGFβ, MAPK/ERK and MAPK/JNK), while expression of two pathway reporters were decreased (Wnt and NFkB) upon miR-181a down-regulation. Notch, Myc/Max, hypoxia and cell cycle/pRB-E2F pathways were not significantly affected ...

  20. Supporting Affect Regulation in Children With Multiple Disabilities During Psychotherapy: A Multiple Case Design Study of Therapeutic Attachment. [Miscellaneous Article

    NARCIS (Netherlands)

    Schuengel, C; Sterkenburg, P S; Jeczynski, P; Janssen, C G C; Jongbloed, G

    2009-01-01

    : In a controlled multiple case design study, the development of a therapeutic relationship and its role in affect regulation were studied in 6 children with visual disabilities, severe intellectual disabilities, severe challenging behavior, and prolonged social deprivation. In the 1st phase,

  1. Dynamics and heterogeneity of brain damage in multiple sclerosis

    KAUST Repository

    Kotelnikova, Ekaterina

    2017-10-26

    Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and degenerative processes that damage the central nervous system (CNS). However, it is not well understood how these events interact and evolve to evoke such a highly dynamic and heterogeneous disease. We established a hypothesis whereby the variability in the course of MS is driven by the very same pathogenic mechanisms responsible for the disease, the autoimmune attack on the CNS that leads to chronic inflammation, neuroaxonal degeneration and remyelination. We propose that each of these processes acts more or less severely and at different times in each of the clinical subgroups. To test this hypothesis, we developed a mathematical model that was constrained by experimental data (the expanded disability status scale [EDSS] time series) obtained from a retrospective longitudinal cohort of 66 MS patients with a long-term follow-up (up to 20 years). Moreover, we validated this model in a second prospective cohort of 120 MS patients with a three-year follow-up, for which EDSS data and brain volume time series were available. The clinical heterogeneity in the datasets was reduced by grouping the EDSS time series using an unsupervised clustering analysis. We found that by adjusting certain parameters, albeit within their biological range, the mathematical model reproduced the different disease courses, supporting the dynamic CNS damage hypothesis to explain MS heterogeneity. Our analysis suggests that the irreversible axon degeneration produced in the early stages of progressive MS is mainly due to the higher rate of myelinated axon degeneration, coupled to the lower capacity for remyelination. However, and in agreement with recent pathological studies, degeneration of chronically demyelinated axons is not a key feature that distinguishes this phenotype. Moreover, the model reveals that lower rates of axon degeneration and more rapid remyelination make relapsing MS more resilient than the

  2. Dynamics and heterogeneity of brain damage in multiple sclerosis

    KAUST Repository

    Kotelnikova, Ekaterina; Kiani, Narsis A.; Abad, Elena; Martinez-Lapiscina, Elena H.; Andorra, Magi; Zubizarreta, Irati; Pulido-Valdeolivas, Irene; Pertsovskaya, Inna; Alexopoulos, Leonidas G.; Olsson, Tomas; Martin, Roland; Paul, Friedemann; Tegner, Jesper; Garcia-Ojalvo, Jordi; Villoslada, Pablo

    2017-01-01

    Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and degenerative processes that damage the central nervous system (CNS). However, it is not well understood how these events interact and evolve to evoke such a highly dynamic and heterogeneous disease. We established a hypothesis whereby the variability in the course of MS is driven by the very same pathogenic mechanisms responsible for the disease, the autoimmune attack on the CNS that leads to chronic inflammation, neuroaxonal degeneration and remyelination. We propose that each of these processes acts more or less severely and at different times in each of the clinical subgroups. To test this hypothesis, we developed a mathematical model that was constrained by experimental data (the expanded disability status scale [EDSS] time series) obtained from a retrospective longitudinal cohort of 66 MS patients with a long-term follow-up (up to 20 years). Moreover, we validated this model in a second prospective cohort of 120 MS patients with a three-year follow-up, for which EDSS data and brain volume time series were available. The clinical heterogeneity in the datasets was reduced by grouping the EDSS time series using an unsupervised clustering analysis. We found that by adjusting certain parameters, albeit within their biological range, the mathematical model reproduced the different disease courses, supporting the dynamic CNS damage hypothesis to explain MS heterogeneity. Our analysis suggests that the irreversible axon degeneration produced in the early stages of progressive MS is mainly due to the higher rate of myelinated axon degeneration, coupled to the lower capacity for remyelination. However, and in agreement with recent pathological studies, degeneration of chronically demyelinated axons is not a key feature that distinguishes this phenotype. Moreover, the model reveals that lower rates of axon degeneration and more rapid remyelination make relapsing MS more resilient than the

  3. Rank Dynamics of Word Usage at Multiple Scales

    Directory of Open Access Journals (Sweden)

    José A. Morales

    2018-05-01

    Full Text Available The recent dramatic increase in online data availability has allowed researchers to explore human culture with unprecedented detail, such as the growth and diversification of language. In particular, it provides statistical tools to explore whether word use is similar across languages, and if so, whether these generic features appear at different scales of language structure. Here we use the Google Books N-grams dataset to analyze the temporal evolution of word usage in several languages. We apply measures proposed recently to study rank dynamics, such as the diversity of N-grams in a given rank, the probability that an N-gram changes rank between successive time intervals, the rank entropy, and the rank complexity. Using different methods, results show that there are generic properties for different languages at different scales, such as a core of words necessary to minimally understand a language. We also propose a null model to explore the relevance of linguistic structure across multiple scales, concluding that N-gram statistics cannot be reduced to word statistics. We expect our results to be useful in improving text prediction algorithms, as well as in shedding light on the large-scale features of language use, beyond linguistic and cultural differences across human populations.

  4. Bubble dynamics under acoustic excitation with multiple frequencies

    International Nuclear Information System (INIS)

    Zhang, Y N; Zhang, Y N; Li, S C

    2015-01-01

    Because of its magnificent mechanical and chemical effects, acoustic cavitation plays an important role in a broad range of biomedical, chemical and mechanical engineering problems. Particularly, irradiation of the multiple frequency acoustic wave could enhance the effects of cavitation. The advantages of employment of multi-frequency ultrasonic field include decreasing the cavitation thresholds, promoting cavitation nuclei generation, increasing the mass transfer and improving energy efficiency. Therefore, multi-frequency ultrasonic systems are employed in a variety of applications, e.g., to enhance the intensity of sonoluminenscence, to increase efficiency of sonochemical reaction, to improve the accuracy of ultrasound imaging and the efficiency of tissue ablation. Compared to single-frequency systems, a lot of new features of bubble dynamics exist in multi-frequency systems, such as special properties of oscillating bubbles, unique resonances in the bubble response curves, and unusual chaotic behaviours. In present paper, the underlying mechanisms of the cavitation effects under multi-frequency acoustical excitation are also briefly introduced

  5. Microprudential Regulation in a Dynamic Model of Banking

    OpenAIRE

    Gianni De Nicolò; Andrea Gamba; Marcella Lucchetta

    2014-01-01

    This paper studies the quantitative impact of microprudential bank regulations on bank lending and value metrics of efficiency and welfare in a dynamic model of banks that are financed by debt and equity, undertake maturity transformation, are exposed to credit and liquidity risks, and face financing frictions. We show that (1) there exists an inverted U-shaped relationship between bank lending, welfare, and capital requirements, (2) liquidity requirements unambiguously reduce lending, effici...

  6. Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Torrealdea Javier

    2011-07-01

    Full Text Available Abstract Background The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS. Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e.g. failure in central tolerance, activation by pathogens that are able to trigger the immune system. Results The model represents five concepts: central tolerance (T-cell generation by the thymus, T-cell activation, T-cell memory, cross-regulation (negative feedback between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system. Conclusion The relapsing dynamic in MS

  7. Dynamic measures of RSA predict distress and regulation in toddlers.

    Science.gov (United States)

    Brooker, Rebecca J; Buss, Kristin A

    2010-05-01

    In this study, we examined a new method for quantifying individual variability using dynamic measures of respiratory sinus arrhythmia (RSA). This method incorporated temporal variation into the measurement of RSA and provided information beyond that offered by more traditional quantifications such as difference scores. Dynamic and static measures of change in RSA were tested in relation to displays of emotion and affective behaviors during a fear-eliciting episode in a sample of 88 typically developing and high-fear toddlers during a laboratory visit at age 24 months. Dynamic measures of RSA contributed information that was unique from traditionally employed, static change scores in predicting high-fear toddlers' displays of shyness during a fear-eliciting episode. In contrast, RSA change scores offered information related to boldness in nonhigh-fear children. In addition, several associations included estimates of nonlinear change in RSA. Implications for the study of individual differences in RSA and relations with emotion and emotion regulation are discussed.

  8. Mouse ribosomal RNA genes contain multiple differentially regulated variants.

    Directory of Open Access Journals (Sweden)

    Hung Tseng

    2008-03-01

    Full Text Available Previous cytogenetic studies suggest that various rDNA chromosomal loci are not equally active in different cell types. Consistent with this variability, rDNA polymorphism is well documented in human and mouse. However, attempts to identify molecularly rDNA variant types, which are regulated individually (i.e., independent of other rDNA variants and tissue-specifically, have not been successful. We report here the molecular cloning and characterization of seven mouse rDNA variants (v-rDNA. The identification of these v-rDNAs was based on restriction fragment length polymorphisms (RFLPs, which are conserved among individuals and mouse strains. The total copy number of the identified variants is less than 100 and the copy number of each individual variant ranges from 4 to 15. Sequence analysis of the cloned v-rDNA identified variant-specific single nucleotide polymorphisms (SNPs in the transcribed region. These SNPs were used to develop a set of variant-specific PCR assays, which permitted analysis of the v-rDNAs' expression profiles in various tissues. These profiles show that three v-rDNAs are expressed in all tissues (constitutively active, two are expressed in some tissues (selectively active, and two are not expressed (silent. These expression profiles were observed in six individuals from three mouse strains, suggesting the pattern is not randomly determined. Thus, the mouse rDNA array likely consists of genetically distinct variants, and some are regulated tissue-specifically. Our results provide the first molecular evidence for cell-type-specific regulation of a subset of rDNA.

  9. TAM receptors regulate multiple features of microglial physiology.

    Science.gov (United States)

    Fourgeaud, Lawrence; Través, Paqui G; Tufail, Yusuf; Leal-Bailey, Humberto; Lew, Erin D; Burrola, Patrick G; Callaway, Perri; Zagórska, Anna; Rothlin, Carla V; Nimmerjahn, Axel; Lemke, Greg

    2016-04-14

    Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells. Here we show that the TAM receptor tyrosine kinases Mer and Axl regulate these microglial functions. We find that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis is normally driven by both TAM receptor ligands Gas6 and protein S. Using live two-photon imaging, we demonstrate that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Finally, we show that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson's disease. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease.

  10. Tyrosine Residues Regulate Multiple Nuclear Functions of P54nrb.

    Science.gov (United States)

    Lee, Ahn R; Hung, Wayne; Xie, Ning; Liu, Liangliang; He, Leye; Dong, Xuesen

    2017-04-01

    The non-POU-domain-containing octamer binding protein (NONO; also known as p54nrb) has various nuclear functions ranging from transcription, RNA splicing, DNA synthesis and repair. Although tyrosine phosphorylation has been proposed to account for the multi-functional properties of p54nrb, direct evidence on p54nrb as a phosphotyrosine protein remains unclear. To investigate the tyrosine phosphorylation status of p54nrb, we performed site-directed mutagenesis on the five tyrosine residues of p54nrb, replacing the tyrosine residues with phenylalanine or alanine, and immunoblotted for tyrosine phosphorylation. We then preceded with luciferase reporter assays, RNA splicing minigene assays, co-immunoprecipitation, and confocal microscopy to study the function of p54nrb tyrosine residues on transcription, RNA splicing, protein-protein interaction, and cellular localization. We found that p54nrb was not phosphorylated at tyrosine residues. Rather, it has non-specific binding affinity to anti-phosphotyrosine antibodies. However, replacement of tyrosine with phenylalanine altered p54nrb activities in transcription co-repression and RNA splicing in gene context-dependent fashions by means of differential regulation of p54nrb protein association with its interacting partners and co-regulators of transcription and splicing. These results demonstrate that tyrosine residues, regardless of phosphorylation status, are important for p54nrb function. J. Cell. Physiol. 232: 852-861, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Optimization of multi-response dynamic systems integrating multiple ...

    African Journals Online (AJOL)

    regression and Taguchi's dynamic signal-to-noise ratio concept ..... algorithm for dynamic multi-response optimization based on goal programming approach. .... problem-solving confirmation, if no grave infringement of model suppositions is ...

  12. Membrane tension regulates clathrin-coated pit dynamics

    Science.gov (United States)

    Liu, Allen

    2014-03-01

    Intracellular organization depends on close communication between the extracellular environment and a network of cytoskeleton filaments. The interactions between cytoskeletal filaments and the plasma membrane lead to changes in membrane tension that in turns help regulate biological processes. Endocytosis is thought to be stimulated by low membrane tension and the removal of membrane increases membrane tension. While it is appreciated that the opposing effects of exocytosis and endocytosis have on keeping plasma membrane tension to a set point, it is not clear how membrane tension affects the dynamics of clathrin-coated pits (CCPs), the individual functional units of clathrin-mediated endocytosis. Furthermore, although it was recently shown that actin dynamics counteracts membrane tension during CCP formation, it is not clear what roles plasma membrane tension plays during CCP initiation. Based on the notion that plasma membrane tension is increased when the membrane area increases during cell spreading, we designed micro-patterned surfaces of different sizes to control the cell spreading sizes. Total internal reflection fluorescence microscopy of living cells and high content image analysis were used to quantify the dynamics of CCPs. We found that there is an increased proportion of CCPs with short (<20s) lifetime for cells on larger patterns. Interestingly, cells on larger patterns have higher CCP initiation density, an effect unexpected based on the conventional view of decreasing endocytosis with increasing membrane tension. Furthermore, by analyzing the intensity profiles of CCPs that were longer-lived, we found CCP intensity decreases with increasing cell size, indicating that the CCPs are smaller with increasing membrane tension. Finally, disruption of actin dynamics significantly increased the number of short-lived CCPs, but also decreased CCP initiation rate. Together, our study reveals new mechanistic insights into how plasma membrane tension regulates

  13. Endothelin-1 Regulation of Exercise-Induced Changes in Flow: Dynamic Regulation of Vascular Tone

    Directory of Open Access Journals (Sweden)

    Robert M. Rapoport

    2017-10-01

    Full Text Available Although endothelin (ET-1 is a highly potent vasoconstrictor with considerable efficacy in numerous vascular beds, the role of endogenous ET-1 in the regulation of vascular tone remains unclear. The perspective that ET-1 plays little role in the on-going regulation of vascular tone at least under physiologic conditions is supported by findings that potential ET-1 constriction is minimized by the release of the vasodilator and ET-1 synthesis inhibitor, nitric oxide (NO. Indeed, ET-1 release and constriction is self-limited by ET-1-induced, endothelial ETB receptor-mediated release of NO. Moreover, even if the balance between ET-1 and NO were reversed as the result of lowered NO activity, as occurs in a number of pathophysiologies associated with endothelial dysfunction, the well-known resistance of ET-1 constriction to reversal (as determined with exogenous ET-1 precludes ET-1 in the dynamic, i.e., moment-to-moment, regulation of vascular tone. On the other hand, and as presently reviewed, findings of ET-1-dependent modulation of organ blood flow with exercise under physiologic conditions demonstrate the dynamic regulation of vascular tone by ET-1. We speculate that this regulation is mediated at least in part through changes in ET-1 synthesis/release caused by pulsatile flow-induced shear stress and NO.

  14. Dynamic berth and quay crane allocation for multiple berth positions and quay cranes

    NARCIS (Netherlands)

    Tri Cahyono, Rully; Flonk, E.J.; Jayawardhana, Bayu

    2015-01-01

    We study in this paper a dynamic berth and quay cranes allocation strategy in general seaport container terminals. We develop a dynamical model that describes the operation of berthing process with multiple discrete berthing positions and multiple quay cranes. Based on the proposed model, we develop

  15. Relaxation dynamics in the presence of pulse multiplicative noise sources with different correlation properties

    Science.gov (United States)

    Kargovsky, A. V.; Chichigina, O. A.; Anashkina, E. I.; Valenti, D.; Spagnolo, B.

    2015-10-01

    The relaxation dynamics of a system described by a Langevin equation with pulse multiplicative noise sources with different correlation properties is considered. The solution of the corresponding Fokker-Planck equation is derived for Gaussian white noise. Moreover, two pulse processes with regulated periodicity are considered as a noise source: the dead-time-distorted Poisson process and the process with fixed time intervals, which is characterized by an infinite correlation time. We find that the steady state of the system is dependent on the correlation properties of the pulse noise. An increase of the noise correlation causes the decrease of the mean value of the solution at the steady state. The analytical results are in good agreement with the numerical ones.

  16. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    International Nuclear Information System (INIS)

    Huang, Er-Wen; Xue, Sheng-Jiang; Li, Xiao-Yan; Xu, Suo-Wen; Cheng, Jian-Ding; Zheng, Jin-Xiang; Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong; Li, Jie; Liu, Chao

    2014-01-01

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma

  17. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Er-Wen [Guangzhou Institute of Forensic Science, Guangzhou (China); Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Xue, Sheng-Jiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Li, Xiao-Yan [Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Suo-Wen [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Cheng, Jian-Ding; Zheng, Jin-Xiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong [Guangzhou Institute of Forensic Science, Guangzhou (China); Li, Jie, E-mail: mdlijie@sina.com [Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, Chao, E-mail: liuchaogaj@21cn.com [Guangzhou Institute of Forensic Science, Guangzhou (China)

    2014-05-02

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

  18. Deficiency of RITA results in multiple mitotic defects by affecting microtubule dynamics.

    Science.gov (United States)

    Steinhäuser, K; Klöble, P; Kreis, N-N; Ritter, A; Friemel, A; Roth, S; Reichel, J M; Michaelis, J; Rieger, M A; Louwen, F; Oswald, F; Yuan, J

    2017-04-01

    Deregulation of mitotic microtubule (MT) dynamics results in defective spindle assembly and chromosome missegregation, leading further to chromosome instability, a hallmark of tumor cells. RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signaling pathway. Intriguingly, deregulated RITA is involved in primary hepatocellular carcinoma and other malignant entities. We were interested in the potential molecular mechanisms behind its involvement. We show here that RITA binds to tubulin and localizes to various mitotic MT structures. RITA coats MTs and affects their structures in vitro as well as in vivo. Tumor cell lines deficient of RITA display increased acetylated α-tubulin, enhanced MT stability and reduced MT dynamics, accompanied by multiple mitotic defects, including chromosome misalignment and segregation errors. Re-expression of wild-type RITA, but not RITA Δtub ineffectively binding to tubulin, restores the phenotypes, suggesting that the role of RITA in MT modulation is mediated via its interaction with tubulin. Mechanistically, RITA interacts with tubulin/histone deacetylase 6 (HDAC6) and its suppression decreases the binding of the deacetylase HDAC6 to tubulin/MTs. Furthermore, the mitotic defects and increased MT stability are also observed in RITA -/- mouse embryonic fibroblasts. RITA has thus a novel role in modulating MT dynamics and its deregulation results in erroneous chromosome segregation, one of the major reasons for chromosome instability in tumor cells.

  19. Dynamic regulation of neurotransmitter specification: Relevance to nervous system homeostasis

    Science.gov (United States)

    Borodinsky, Laura N.; Belgacem, Yesser Hadj; Swapna, Immani; Sequerra, Eduardo Bouth

    2013-01-01

    During nervous system development the neurotransmitter identity changes and coexpression of several neurotransmitters is a rather generalized feature of developing neurons. In the mature nervous system, different physiological and pathological circumstances recreate this phenomenon. The rules of neurotransmitter respecification are multiple. Among them, the goal of assuring balanced excitability appears as an important driving force for the modifications in neurotransmitter phenotype expression. The functional consequences of these dynamic revisions in neurotransmitter identity span a varied range, from fine-tuning the developing neural circuit to modifications in addictive and locomotor behaviors. Current challenges include determining the mechanisms underlying neurotransmitter phenotype respecification and how they intersect with genetic programs of neuronal specialization. PMID:23270605

  20. Dynamic regulation of the endocannabinoid system: implications for analgesia

    Directory of Open Access Journals (Sweden)

    Wong Amy

    2009-10-01

    Full Text Available Abstract The analgesic effects of cannabinoids are well documented, but these are often limited by psychoactive side-effects. Recent studies indicate that the endocannabinoid system is dynamic and altered under different pathological conditions, including pain states. Changes in this receptor system include altered expression of receptors, differential synthetic pathways for endocannabinoids are expressed by various cell types, multiple pathways of catabolism and the generation of biologically active metabolites, which may be engaged under different conditions. This review discusses the evidence that pain states alter the endocannabinoid receptor system at key sites involved in pain processing and how these changes may inform the development of cannabinoid-based analgesics.

  1. Dynamics Analysis for Hydroturbine Regulating System Based on Matrix Model

    Directory of Open Access Journals (Sweden)

    Jiafu Wei

    2017-01-01

    Full Text Available The hydraulic turbine model is the key factor which affects the analysis precision of the hydraulic turbine governing system. This paper discusses the basic principle of the hydraulic turbine matrix model and gives two methods to realize. Using the characteristic matrix to describe unit flow and torque and their relationship with the opening and unit speed, it can accurately represent the nonlinear characteristics of the turbine, effectively improve the convergence of simulation process, and meet the needs of high precision real-time simulation of power system. Through the simulation of a number of power stations, it indicates that, by analyzing the dynamic process of the hydraulic turbine regulating with 5-order matrix model, the calculation results and field test data will have good consistency, and it can better meet the needs of power system dynamic simulation.

  2. The dynamic regulation of NAD metabolism in mitochondria

    Science.gov (United States)

    Stein, Liana Roberts; Imai, Shin-ichiro

    2012-01-01

    Mitochondria are intracellular powerhouses that produce ATP and carry out diverse functions for cellular energy metabolism. While the maintenance of an optimal NAD/NADH ratio is essential for mitochondrial function, it has recently become apparent that the maintenance of the mitochondrial NAD pool also has critical importance. The biosynthesis, transport, and catabolism of NAD and its key intermediates play an important role in the regulation of NAD-consuming mediators, such as sirtuins, poly-ADP-ribose polymerases, and CD38/157 ectoenzymes, in intra- and extracellular compartments. Mitochondrial NAD biosynthesis is also modulated in response to nutritional and environmental stimuli. In this article, we discuss this dynamic regulation of NAD metabolism in mitochondria to shed light on the intimate connection between NAD and mitochondrial function. PMID:22819213

  3. Dynamic regulation of hepatic lipid droplet properties by diet.

    Science.gov (United States)

    Crunk, Amanda E; Monks, Jenifer; Murakami, Aya; Jackman, Matthew; Maclean, Paul S; Ladinsky, Mark; Bales, Elise S; Cain, Shannon; Orlicky, David J; McManaman, James L

    2013-01-01

    Cytoplasmic lipid droplets (CLD) are organelle-like structures that function in neutral lipid storage, transport and metabolism through the actions of specific surface-associated proteins. Although diet and metabolism influence hepatic CLD levels, how they affect CLD protein composition is largely unknown. We used non-biased, shotgun, proteomics in combination with metabolic analysis, quantitative immunoblotting, electron microscopy and confocal imaging to define the effects of low- and high-fat diets on CLD properties in fasted-refed mice. We found that the hepatic CLD proteome is distinct from that of CLD from other mammalian tissues, containing enzymes from multiple metabolic pathways. The hepatic CLD proteome is also differentially affected by dietary fat content and hepatic metabolic status. High fat feeding markedly increased the CLD surface density of perilipin-2, a critical regulator of hepatic neutral lipid storage, whereas it reduced CLD levels of betaine-homocysteine S-methyltransferase, an enzyme regulator of homocysteine levels linked to fatty liver disease and hepatocellular carcinoma. Collectively our data demonstrate that the hepatic CLD proteome is enriched in metabolic enzymes, and that it is qualitatively and quantitatively regulated by diet and metabolism. These findings implicate CLD in the regulation of hepatic metabolic processes, and suggest that their properties undergo reorganization in response to hepatic metabolic demands.

  4. Environmental regulation and the export dynamics of energy technologies

    International Nuclear Information System (INIS)

    Costantini, Valeria; Crespi, Francesco

    2008-01-01

    The pollution haven hypothesis affirms that an open market regime will encourage the flow of low-technology polluting industries towards developing countries because of potential comparative advantages related to low environmental standards. In contrast, the hypothesis suggested by Porter and van der Linde claims that innovating firms operate in a dynamic competitive situation which allows global diffusion of environmental-friendly technologies. Environmental regulation may represent a relevant mechanism through which technological change is induced. In this way, countries that are subject to more stringent environmental regulations may become net exporters of environmental technologies. This paper provides new evidence on the evolution of export flows of environmental technologies across different countries for the energy sector. Advanced economies, particularly the European Union, have increasingly focused on the role of energy policies as tools for sustaining the development path. The Kyoto Protocol commitments, together with growing import dependence on energy products, have brought attention to the analysis of innovation processes in this specific sector. The analysis uses a gravity model in order to test the determinants and the transmission channels through which environmental technologies for renewable energies and energy efficiency are exported to advanced and developing countries. Our results are consistent with the Porter and van der Linde hypothesis where environmental regulation represents a significant source of comparative advantages. What strongly emerges is that the stringency of environmental regulation supplemented by the strength of the National Innovation System is a crucial driver of export performance in the field of energy technologies. (author)

  5. Multiple equilibria and limit cycles in evolutonary games with Logit Dynamics

    NARCIS (Netherlands)

    Hommes, C.H.; Ochea, M.I.

    2012-01-01

    This note shows, by means of two simple, three-strategy games, the existence of stable periodic orbits and of multiple, interior steady states in a smooth version of the Best-Response Dynamics, the Logit Dynamics. The main finding is that, unlike Replicator Dynamics, generic Hopf bifurcation and

  6. Reconstructing a Network of Stress-Response Regulators via Dynamic System Modeling of Gene Regulation

    Directory of Open Access Journals (Sweden)

    Wei-Sheng Wu

    2008-01-01

    Full Text Available Unicellular organisms such as yeasts have evolved mechanisms to respond to environmental stresses by rapidly reorganizing the gene expression program. Although many stress-response genes in yeast have been discovered by DNA microarrays, the stress-response transcription factors (TFs that regulate these stress-response genes remain to be investigated. In this study, we use a dynamic system model of gene regulation to describe the mechanism of how TFs may control a gene’s expression. Then, based on the dynamic system model, we develop the Stress Regulator Identification Algorithm (SRIA to identify stress-response TFs for six kinds of stresses. We identified some general stress-response TFs that respond to various stresses and some specific stress-response TFs that respond to one specifi c stress. The biological significance of our findings is validated by the literature. We found that a small number of TFs is probably suffi cient to control a wide variety of expression patterns in yeast under different stresses. Two implications can be inferred from this observation. First, the response mechanisms to different stresses may have a bow-tie structure. Second, there may be regulatory cross-talks among different stress responses. In conclusion, this study proposes a network of stress-response regulators and the details of their actions.

  7. Fast Responding Voltage Regulator and Dynamic VAR Compensator

    Energy Technology Data Exchange (ETDEWEB)

    Divan, Deepak [Varentec, Incorporated, San Jose, CA (United States); Moghe, Rohit [Varentec, Incorporated, San Jose, CA (United States); Tholomier, Damien [Varentec, Incorporated, San Jose, CA (United States)

    2014-12-31

    The objectives of this project were to develop a dynamic VAR compensator (DVC) for voltage regulation through VAR support to demonstrate the ability to achieve greater levels of voltage control on electricity distribution networks, and faster response compared to existing grid technology. The goal of the project was to develop a prototype Fast Dynamic VAR Compensator (Fast DVC) hardware device, and this was achieved. In addition to developing the dynamic VAR compensator device, Varentec in partnership with researchers at North Carolina State University (NCSU) successfully met the objectives to model the potential positive impact of such DVCs on representative power networks. This modeling activity validated the ability of distributed dynamic VAR compensators to provide fast voltage regulation and reactive power control required to respond to grid disturbances under high penetration of fluctuating and intermittent distributed energy resources (DERs) through extensive simulation studies. Specifically the following tasks were set to be accomplished: 1) Development of dynamic VAR compensator to support dynamic voltage variations on the grid through VAR control 2) Extensive testing of the DVC in the lab environment 3) Present the operational DVC device to the DOE at Varentec’s lab 4) Formulation of a detailed specification sheet, unit assembly document, test setup document, unit bring-up plan, and test plan 5) Extensive simulations of the DVC in a system with high PV penetration. Understanding the operation with many DVC on a single distribution system 6) Creation and submittal of quarterly and final reports conveying the design documents, unit performance data, modeling simulation charts and diagrams, and summary explanations of the satisfaction of program goals. This report details the various efforts that led to the development of the Fast DVC as well as the modeling & simulation results. The report begins with the introduction in Section II which outlines the

  8. MMSET is dynamically regulated during cell-cycle progression and promotes normal DNA replication.

    Science.gov (United States)

    Evans, Debra L; Zhang, Haoxing; Ham, Hyoungjun; Pei, Huadong; Lee, SeungBaek; Kim, JungJin; Billadeau, Daniel D; Lou, Zhenkun

    2016-01-01

    The timely and precise duplication of cellular DNA is essential for maintaining genome integrity and is thus tightly-regulated. During mitosis and G1, the Origin Recognition Complex (ORC) binds to future replication origins, coordinating with multiple factors to load the minichromosome maintenance (MCM) complex onto future replication origins as part of the pre-replication complex (pre-RC). The pre-RC machinery, in turn, remains inactive until the subsequent S phase when it is required for replication fork formation, thereby initiating DNA replication. Multiple myeloma SET domain-containing protein (MMSET, a.k.a. WHSC1, NSD2) is a histone methyltransferase that is frequently overexpressed in aggressive cancers and is essential for normal human development. Several studies have suggested a role for MMSET in cell-cycle regulation; however, whether MMSET is itself regulated during cell-cycle progression has not been examined. In this study, we report that MMSET is degraded during S phase in a cullin-ring ligase 4-Cdt2 (CRL4(Cdt2)) and proteasome-dependent manner. Notably, we also report defects in DNA replication and a decreased association of pre-RC factors with chromatin in MMSET-depleted cells. Taken together, our results suggest a dynamic regulation of MMSET levels throughout the cell cycle, and further characterize the role of MMSET in DNA replication and cell-cycle progression.

  9. CGGBP1-CTCF dynamics in regulation of chromosomal interactions

    Directory of Open Access Journals (Sweden)

    Divyesh Patel

    2017-10-01

    Full Text Available Genome organisation and gene expression is regulated by specific DNA sequences that include “insulator elements”. Insulator proteins, such as CTCF bind to insulator elements to block spreading of silent chromatin in-cis or inhibit interactions between transcriptional enhancers and promoters. By binding to insulators in a methylation-sensittive manner, CTCF establishes and maintains contrasting transcription patterns on either side of the insulator elements [1]. Though details of CTCF-insulator activities have been worked out, mechanisms of regulation of insulator activity by other proteins is unknown. CTCF-binding insulators are retrotransposon-derived, the same elements to which CGGBP1 binds making CGGBP1 a candidate insulator regulator factor [2]. Objective is to explore role of CGGBP1-CTCF dynamics in regulation of insulator activity. 1064Sk skin fibroblasts were grown in presence or absence of CGGBP1 in growth stimulated or starved condition. ChIP-seq was performed to identify CGGBP1-binding DNA sequence motifs [3]. We have observed a strong overlap between binding sites of CTCF and CGGBP1 [4, 5].  CGGBP1 and CTCF seem to share the retrotransposons-derived M1 and M2 motifs. Unlike in quiescent cells, growth factor-stimulation increased CGGBP1 binding to CTCF-CGGBP1 binding sites with decreased CTCF insulator activity. The distance between CGGBP1 M1 and M2 motifs was longer in quiescent cells as compared to growth stimulated cells. Our results suggest that CGGBP1 negatively regulates CTCF insulator activity in normal cells in a growth signal-dependent manner.

  10. Vorticity Dynamics in Single and Multiple Swirling Reacting Jets

    Science.gov (United States)

    Smith, Travis; Aguilar, Michael; Emerson, Benjamin; Noble, David; Lieuwen, Tim

    2015-11-01

    This presentation describes an analysis of the unsteady flow structures in two multinozzle swirling jet configurations. This work is motivated by the problem of combustion instabilities in premixed flames, a major concern in the development of modern low NOx combustors. The objective is to compare the unsteady flow structures in these two configurations for two separate geometries and determine how certain parameters, primarily distance between jets, influence the flow dynamics. The analysis aims to differentiate between the flow dynamics of single nozzle and triple nozzle configurations. This study looks at how the vorticity in the shear layers of one reacting swirling jet can affect the dynamics of a nearby similar jet. The distance between the swirling jets is found to have an effect on the flow field in determining where swirling jets merge and on the dynamics upstream of the merging location. Graduate Student, School of Aerospace Engineering, Georgia Institute of Technology, Atlanta, GA.

  11. Precise regulation of gene expression dynamics favors complex promoter architectures.

    Directory of Open Access Journals (Sweden)

    Dirk Müller

    2009-01-01

    Full Text Available Promoters process signals through recruitment of transcription factors and RNA polymerase, and dynamic changes in promoter activity constitute a major noise source in gene expression. However, it is barely understood how complex promoter architectures determine key features of promoter dynamics. Here, we employ prototypical promoters of yeast ribosomal protein genes as well as simplified versions thereof to analyze the relations among promoter design, complexity, and function. These promoters combine the action of a general regulatory factor with that of specific transcription factors, a common motif of many eukaryotic promoters. By comprehensively analyzing stationary and dynamic promoter properties, this model-based approach enables us to pinpoint the structural characteristics underlying the observed behavior. Functional tradeoffs impose constraints on the promoter architecture of ribosomal protein genes. We find that a stable scaffold in the natural design results in low transcriptional noise and strong co-regulation of target genes in the presence of gene silencing. This configuration also exhibits superior shut-off properties, and it can serve as a tunable switch in living cells. Model validation with independent experimental data suggests that the models are sufficiently realistic. When combined, our results offer a mechanistic explanation for why specific factors are associated with low protein noise in vivo. Many of these findings hold for a broad range of model parameters and likely apply to other eukaryotic promoters of similar structure.

  12. The Temporal Dynamics of Arc Expression Regulate Cognitive Flexibility.

    Science.gov (United States)

    Wall, Mark J; Collins, Dawn R; Chery, Samantha L; Allen, Zachary D; Pastuzyn, Elissa D; George, Arlene J; Nikolova, Viktoriya D; Moy, Sheryl S; Philpot, Benjamin D; Shepherd, Jason D; Müller, Jürgen; Ehlers, Michael D; Mabb, Angela M; Corrêa, Sonia A L

    2018-05-24

    Neuronal activity regulates the transcription and translation of the immediate-early gene Arc/Arg3.1, a key mediator of synaptic plasticity. Proteasome-dependent degradation of Arc tightly limits its temporal expression, yet the significance of this regulation remains unknown. We disrupted the temporal control of Arc degradation by creating an Arc knockin mouse (ArcKR) where the predominant Arc ubiquitination sites were mutated. ArcKR mice had intact spatial learning but showed specific deficits in selecting an optimal strategy during reversal learning. This cognitive inflexibility was coupled to changes in Arc mRNA and protein expression resulting in a reduced threshold to induce mGluR-LTD and enhanced mGluR-LTD amplitude. These findings show that the abnormal persistence of Arc protein limits the dynamic range of Arc signaling pathways specifically during reversal learning. Our work illuminates how the precise temporal control of activity-dependent molecules, such as Arc, regulates synaptic plasticity and is crucial for cognition. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  13. EWSR1 regulates mitosis by dynamically influencing microtubule acetylation.

    Science.gov (United States)

    Wang, Yi-Long; Chen, Hui; Zhan, Yi-Qun; Yin, Rong-Hua; Li, Chang-Yan; Ge, Chang-Hui; Yu, Miao; Yang, Xiao-Ming

    2016-08-17

    EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with α-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycle-dependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.

  14. Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma.

    Directory of Open Access Journals (Sweden)

    Javad Salimi Sartakhti

    Full Text Available Cancer cells and stromal cells cooperate by exchanging diffusible factors that sustain tumor growth, a form of frequency-dependent selection that can be studied in the framework of evolutionary game theory. In the case of multiple myeloma, three types of cells (malignant plasma cells, osteoblasts and osteoclasts exchange growth factors with different effects, and tumor-stroma interactions have been analysed using a model of cooperation with pairwise interactions. Here we show that a model in which growth factors have autocrine and paracrine effects on multiple cells, a more realistic assumption for tumor-stroma interactions, leads to different results, with implications for disease progression and treatment. In particular, the model reveals that reducing the number of malignant plasma cells below a critical threshold can lead to their extinction and thus to restore a healthy balance between osteoclast and osteoblast, a result in line with current therapies against multiple myeloma.

  15. Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator.

    Science.gov (United States)

    Casino, Patricia; Miguel-Romero, Laura; Huesa, Juanjo; García, Pablo; García-Del Portillo, Francisco; Marina, Alberto

    2018-01-09

    The RcsCDB phosphorelay system controls an extremely large regulon in Enterobacteriaceae that involves processes such as biofilm formation, flagella production, synthesis of extracellular capsules and cell division. Therefore, fine-tuning of this system is essential for virulence in pathogenic microorganisms of this group. The final master effector of the RcsCDB system is the response regulator (RR) RcsB, which activates or represses multiple genes by binding to different promoter regions. This regulatory activity of RcsB can be done alone or in combination with additional transcriptional factors in phosphorylated or dephosphorylated states. The capacity of RcsB to interact with multiple promoters and partners, either dephosphorylated or phosphorylated, suggests an extremely conformational dynamism for this RR. To shed light on the activation mechanism of RcsB and its implication on promoter recognition, we solved the crystal structure of full-length RcsB from Salmonella enterica serovar Typhimurium in the presence and absence of a phosphomimetic molecule BeF3-. These two novel structures have guided an extensive site-directed mutagenesis study at the structural and functional level that confirms RcsB conformational plasticity and dynamism. Our data allowed us to propose a β5-T switch mechanism where phosphorylation is coupled to alternative DNA binding ways and which highlights the conformational dynamism of RcsB to be so pleiotropic. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Multiple time scale dynamics in the breakdown of superhydrophobicity

    NARCIS (Netherlands)

    Pirat, C.; Sbragaglia, M.; Peters, A.M.; Borkent, B.M.; Lammertink, Rob G.H.; Wessling, Matthias; Lohse, Detlef

    2008-01-01

    Drops deposited on rough and hydrophobic surfaces can stay suspended with gas pockets underneath the liquid, then showing very low hydrodynamic resistance. When this superhydrophobic state breaks down, the subsequent wetting process can show different dynamical properties. A suitable choice of the

  17. Sequencing dynamic storage systems with multiple lifts and shuttles

    NARCIS (Netherlands)

    Carlo, Hector J.; Vis, Iris F. A.

    2012-01-01

    New types of Automated Storage and Retrieval Systems (AS/RS) able to achieve high throughput are continuously being developed and require new control polices to take full advantage of the developed system. In this paper, a dynamic storage system has been studied as developed by Vanderlande

  18. Free energy from molecular dynamics with multiple constraints

    NARCIS (Netherlands)

    den Otter, Wouter K.; Briels, Willem J.

    2000-01-01

    In molecular dynamics simulations of reacting systems, the key step to determining the equilibrium constant and the reaction rate is the calculation of the free energy as a function of the reaction coordinate. Intuitively the derivative of the free energy is equal to the average force needed to

  19. Expression of the central growth regulator BIG BROTHER is regulated by multiple cis-elements

    Directory of Open Access Journals (Sweden)

    Breuninger Holger

    2012-03-01

    Full Text Available Abstract Background Much of the organismal variation we observe in nature is due to differences in organ size. The observation that even closely related species can show large, stably inherited differences in organ size indicates a strong genetic component to the control of organ size. Despite recent progress in identifying factors controlling organ growth in plants, our overall understanding of this process remains limited, partly because the individual factors have not yet been connected into larger regulatory pathways or networks. To begin addressing this aim, we have studied the upstream regulation of expression of BIG BROTHER (BB, a central growth-control gene in Arabidopsis thaliana that prevents overgrowth of organs. Final organ size and BB expression levels are tightly correlated, implying the need for precise control of its expression. BB expression mirrors proliferative activity, yet the gene functions to limit proliferation, suggesting that it acts in an incoherent feedforward loop downstream of growth activators to prevent over-proliferation. Results To investigate the upstream regulation of BB we combined a promoter deletion analysis with a phylogenetic footprinting approach. We were able to narrow down important, highly conserved, cis-regulatory elements within the BB promoter. Promoter sequences of other Brassicaceae species were able to partially complement the A. thaliana bb-1 mutant, suggesting that at least within the Brassicaceae family the regulatory pathways are conserved. Conclusions This work underlines the complexity involved in precise quantitative control of gene expression and lays the foundation for identifying important upstream regulators that determine BB expression levels and thus final organ size.

  20. Information-flux approach to multiple-spin dynamics

    International Nuclear Information System (INIS)

    Di Franco, C.; Paternostro, M.; Kim, M. S.; Palma, G. M.

    2007-01-01

    We introduce and formalize the concept of information flux in a many-body register as the influence that the dynamics of a specific element receive from any other element of the register. By quantifying the information flux in a protocol, we can design the most appropriate initial state of the system and, noticeably, the distribution of coupling strengths among the parts of the register itself. The intuitive nature of this tool and its flexibility, which allow for easily manageable numerical approaches when analytic expressions are not straightforward, are greatly useful in interacting many-body systems such as quantum spin chains. We illustrate the use of this concept in quantum cloning and quantum state transfer and we also sketch its extension to nonunitary dynamics

  1. Collision avoidance for multiple Lagrangian dynamical systems with gyroscopic forces

    Directory of Open Access Journals (Sweden)

    Lorenzo Sabattini

    2017-01-01

    Full Text Available This article introduces a novel methodology for dealing with collision avoidance for groups of mobile robots. In particular, full dynamics are considered, since each robot is modeled as a Lagrangian dynamical system moving in a three-dimensional environment. Gyroscopic forces are utilized for defining the collision avoidance control strategy: This kind of forces leads to avoiding collisions, without interfering with the convergence properties of the multi-robot system’s desired control law. Collision avoidance introduces, in fact, a perturbation on the nominal behavior of the system: We define a method for choosing the direction of the gyroscopic force in an optimal manner, in such a way that perturbation is minimized. Collision avoidance and convergence properties are analytically demonstrated, and simulation results are provided for validation purpose.

  2. Competitive Pressure: Competitive Dynamics as Reactions to Multiple Rivals

    OpenAIRE

    Zucchini, Leon; Kretschmer, Tobias

    2011-01-01

    Competitive dynamics research has focused primarily on interactions between dyads of firms. Drawing on the awareness-motivation-capability framework and strategic group theory we extend this by proposing that firms’ actions are influenced by perceived competitive pressure resulting from actions by several rivals. We predict that firms’ action magnitude is influenced by the total number of rival actions accumulating in the market, and that this effect is moderated by strategic group membership...

  3. Dynamic pipe control with a multiple digit automatic measuring device

    International Nuclear Information System (INIS)

    Jenzer, P.

    1984-01-01

    With the flow rotating method, thin-walled pipes can be produced with very tight tolerances and high mechanical sturdiness. The measuring device permits a dynamic control of these pipes, the outer diameter of which can lie between 70 and 300 mm, the length between 500 and 2000 mm and the wall thickness between 0,5 and 10 mm. Depending on the pipe type, up to 27 measurements in a maximum of 5 measuring levels are to be controlled. (orig.) [de

  4. Dynamic capabilities and innovation: a Multiple-Case Study

    OpenAIRE

    Bravo Ibarra, Edna Rocío; Mundet Hiern, Joan; Suñé Torrents, Albert

    2009-01-01

    After a detailed survey of the scientific literature, it was found that several characteristics of dynamic capabilities were similar to those of innovation capability. Therefore, with a deeper study of the first ones, it could be possible to design a model aimed to structure innovation capability. Thus, this work presents a conceptual model, where the innovation capability is shown as result of three processes: knowledge absorption and creation capability, knowledge integration and knowledge ...

  5. Multi-Equilibria Regulation Agent-Based Model of Opinion Dynamics in Social Networks

    Directory of Open Access Journals (Sweden)

    Andreas Koulouris

    2013-01-01

    Full Text Available This article investigates the Multiple Equilibria Regulation (MER model, i.e., an agent-based simulation model, to represent opinion dynamics in social networks. It relies on a small set of micro-prerequisites (intra-individual balance and confidence bound, leading to emergence of (nonstationary macro-outcomes. These outcomes may refer to consensus, polarization or fragmentation of opinions about taxation (e.g., congestion pricing or other policy measures, according to the way communication is structured. In contrast with other models of opinion dynamics, it allows for the impact of both the regulation of intra-personal discrepancy and the interpersonal variability of opinions on social learning and network dynamics. Several simulation experiments are presented to demonstrate, through the MER model, the role of different network structures (complete, star, cellular automata, small-world and random graphs on opinion formation dynamics and the overall evolution of the system. The findings can help to identify specific topological characteristics, such as density, number of neighbourhoods and critical nodes-agents, that affect the stability and system dynamics. This knowledge can be used to better organize the information diffusion and learning in the community, enhance the predictability of outcomes and manage possible conflicts. It is shown that a small-world organization, which depicts more realistic aspects of real-life and virtual social systems, provides increased predictability and stability towards a less fragmented and more manageable grouping of opinions, compared to random networks. Such macro-level organizations may be enhanced with use of web-based technologies to increase the density of communication and public acceptability of policy measures.

  6. Modelling the Dynamics of Intracellular Processes as an Organisation of Multiple Agents

    NARCIS (Netherlands)

    Bosse, T.; Jonker, C.M.; Treur, J.; Armano, G.; Merelli, E.; Denzinger, J.; Martin, A.; Miles, S.; Tianfield, H.; Unland, R.

    2005-01-01

    This paper explores how the dynamics of complex biological processes can be modeled as an organisation of multiple agents. This modelling perspective identifies organisational structure occurring in complex decentralised processes and handles complexity of the analysis of the dynamics by structuring

  7. Conformational Rigidity and Protein Dynamics at Distinct Timescales Regulate PTP1B Activity and Allostery.

    Science.gov (United States)

    Choy, Meng S; Li, Yang; Machado, Luciana E S F; Kunze, Micha B A; Connors, Christopher R; Wei, Xingyu; Lindorff-Larsen, Kresten; Page, Rebecca; Peti, Wolfgang

    2017-02-16

    Protein function originates from a cooperation of structural rigidity, dynamics at different timescales, and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in Protein Tyrosine Phosphatase 1B (PTP1B), a drug target for diabetes and cancer that catalyzes the dephosphorylation of numerous substrates in essential signaling pathways. By combining new experimental and computational data on WT-PTP1B and ≥10 PTP1B variants in multiple states, we discovered a fundamental and evolutionarily conserved CH/π switch that is critical for positioning the catalytically important WPD loop. Furthermore, our data show that PTP1B uses conformational and dynamic allostery to regulate its activity. This shows that both conformational rigidity and dynamics are essential for controlling protein activity. This connection between rigidity and dynamics at different timescales is likely a hallmark of all enzyme function. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Dynamics of the Greenland Ice Sheet over multiple timescales

    DEFF Research Database (Denmark)

    Kjeldsen, Kristian Kjellerup

    to further constrain the individual components of the current budget, and in conjunction with longer records, it is important to provide a trustworthy basis for future projections. In this thesis, using airborne- and satellite derived data combined with terrestrial and marine observations, the dynamic...... become grounded and also assuming a similar warming pattern. This thesis implies that in order to investigate the response of the Greenland Ice Sheet to future climate change much is to be gained by merging and incorporating data from both marine and terrestrial geology, combined with air- and satellite...

  9. LIBVERSIONINGCOMPILER: An easy-to-use library for dynamic generation and invocation of multiple code versions

    Science.gov (United States)

    Cherubin, S.; Agosta, G.

    2018-01-01

    We present LIBVERSIONINGCOMPILER, a C++ library designed to support the dynamic generation of multiple versions of the same compute kernel in a HPC scenario. It can be used to provide continuous optimization, code specialization based on the input data or on workload changes, or otherwise to dynamically adjust the application, without the burden of a full dynamic compiler. The library supports multiple underlying compilers but specifically targets the LLVM framework. We also provide examples of use, showing the overhead of the library, and providing guidelines for its efficient use.

  10. Emotion regulation and the dynamics of feelings: A conceptual and methodological framework [IF: 3.3

    OpenAIRE

    Hoeksma, J.B.; Oosterlaan, J.; Schipper, E.M.

    2004-01-01

    The emotional system is defined as a dynamical system that has neurological and biochemical structures that force the system to change in a regular and consistent way. This dynamic view allows for an alternative definition of emotion regulation, which describes when emotion regulation is needed, identifies its goal, and illustrates how regulation is achieved. The thesis developed here is that feelings - the private mental experience of emotion - play a crucial role in emotion regulation. Spec...

  11. Emotion regulation and the dynamic of feelings: A conceptual and methodological framework

    OpenAIRE

    Hoeksma, J.B.; Oosterlaan, J.; Schipper, E.

    2004-01-01

    The emotional system is defined as a dynamical system that has neurological and biochemical structures that force the system to change in a regular and consistent way. This dynamic view allows for an alternative definition of emotion regulation, which describes when emotion regulation is needed, identifies its goal, and illustrates how regulation is achieved. The thesis developed here is that feelings - the private mental experience of emotion - play a crucial role in emotion regulation. Spec...

  12. Dynamic information architecture system (DIAS) : multiple model simulation management

    International Nuclear Information System (INIS)

    Simunich, K. L.; Sydelko, P.; Dolph, J.; Christiansen, J.

    2002-01-01

    Dynamic Information Architecture System (DIAS) is a flexible, extensible, object-based framework for developing and maintaining complex multidisciplinary simulations of a wide variety of application contexts. The modeling domain of a specific DIAS-based simulation is determined by (1) software Entity (domain-specific) objects that represent the real-world entities that comprise the problem space (atmosphere, watershed, human), and (2) simulation models and other data processing applications that express the dynamic behaviors of the domain entities. In DIAS, models communicate only with Entity objects, never with each other. Each Entity object has a number of Parameter and Aspect (of behavior) objects associated with it. The Parameter objects contain the state properties of the Entity object. The Aspect objects represent the behaviors of the Entity object and how it interacts with other objects. DIAS extends the ''Object'' paradigm by abstraction of the object's dynamic behaviors, separating the ''WHAT'' from the ''HOW.'' DIAS object class definitions contain an abstract description of the various aspects of the object's behavior (the WHAT), but no implementation details (the HOW). Separate DIAS models/applications carry the implementation of object behaviors (the HOW). Any model deemed appropriate, including existing legacy-type models written in other languages, can drive entity object behavior. The DIAS design promotes plug-and-play of alternative models, with minimal recoding of existing applications. The DIAS Context Builder object builds a constructs or scenario for the simulation, based on developer specification and user inputs. Because DIAS is a discrete event simulation system, there is a Simulation Manager object with which all events are processed. Any class that registers to receive events must implement an event handler (method) to process the event during execution. Event handlers can schedule other events; create or remove Entities from the

  13. Dynamic information architecture system (DIAS) : multiple model simulation management.

    Energy Technology Data Exchange (ETDEWEB)

    Simunich, K. L.; Sydelko, P.; Dolph, J.; Christiansen, J.

    2002-05-13

    Dynamic Information Architecture System (DIAS) is a flexible, extensible, object-based framework for developing and maintaining complex multidisciplinary simulations of a wide variety of application contexts. The modeling domain of a specific DIAS-based simulation is determined by (1) software Entity (domain-specific) objects that represent the real-world entities that comprise the problem space (atmosphere, watershed, human), and (2) simulation models and other data processing applications that express the dynamic behaviors of the domain entities. In DIAS, models communicate only with Entity objects, never with each other. Each Entity object has a number of Parameter and Aspect (of behavior) objects associated with it. The Parameter objects contain the state properties of the Entity object. The Aspect objects represent the behaviors of the Entity object and how it interacts with other objects. DIAS extends the ''Object'' paradigm by abstraction of the object's dynamic behaviors, separating the ''WHAT'' from the ''HOW.'' DIAS object class definitions contain an abstract description of the various aspects of the object's behavior (the WHAT), but no implementation details (the HOW). Separate DIAS models/applications carry the implementation of object behaviors (the HOW). Any model deemed appropriate, including existing legacy-type models written in other languages, can drive entity object behavior. The DIAS design promotes plug-and-play of alternative models, with minimal recoding of existing applications. The DIAS Context Builder object builds a constructs or scenario for the simulation, based on developer specification and user inputs. Because DIAS is a discrete event simulation system, there is a Simulation Manager object with which all events are processed. Any class that registers to receive events must implement an event handler (method) to process the event during execution. Event handlers

  14. Multiple ionization dynamics of molecules in intense laser fields

    International Nuclear Information System (INIS)

    Ichimura, Atsushi; Ohyama-Yamaguchi, Tomoko

    2005-01-01

    A classical field-ionization model is developed for sequential multiple ionization of diatomic and linear triatomic molecules exposed to intense (∼ 10 15 W/cm 2 ) laser fields. The distance R ion of Coulomb explosion is calculated for a combination of fragment charges, by considering nonadiabatic excitation followed by field ionization associated with the inner and outer saddle points. For diatomic molecules (N 2 , NO, and I 2 ), the model explains behaviors observed in experiments, as R ion (21→31) ion (21→22) between competing charge-asymmetric and symmetric channels, and even-odd fluctuation along a principal pathway. For a triatomic molecule CO 2 , a comparison of the model with an experiment suggests that charge-symmetric (or nearly symmetric) channels are dominantly populated. (author)

  15. Focal dynamics of multiple filaments: Microscopic imaging and reconstruction

    International Nuclear Information System (INIS)

    Kiran, P. Prem; Bagchi, Suman; Kumar, G. Ravindra; Krishnan, Siva Rama; Arnold, C. L.; Couairon, A.

    2010-01-01

    We observe the complete dynamics of the propagation of very intense, femtosecond laser pulses in air under tight focusing conditions via direct imaging of the entire interaction zone. The whole life history of the focused pulses is then reconstructed by means of numerical simulations. We show that beam breakup leads to a dual-rate increase in filament numbers with laser power. Linearly and circularly polarized pulses give rise to beam breakup and fusion governed by external focusing conditions. For tight focusing conditions, intensity saturation due to plasma generation and nonlinear losses does not limit the intensity growth, thereby giving access to a new propagation regime featured by an efficient laser energy deposition in fully ionized air and intense 10 15 W/cm 2 pulses at the focus.

  16. A quantitative and dynamic model for plant stem cell regulation.

    Directory of Open Access Journals (Sweden)

    Florian Geier

    Full Text Available Plants maintain pools of totipotent stem cells throughout their entire life. These stem cells are embedded within specialized tissues called meristems, which form the growing points of the organism. The shoot apical meristem of the reference plant Arabidopsis thaliana is subdivided into several distinct domains, which execute diverse biological functions, such as tissue organization, cell-proliferation and differentiation. The number of cells required for growth and organ formation changes over the course of a plants life, while the structure of the meristem remains remarkably constant. Thus, regulatory systems must be in place, which allow for an adaptation of cell proliferation within the shoot apical meristem, while maintaining the organization at the tissue level. To advance our understanding of this dynamic tissue behavior, we measured domain sizes as well as cell division rates of the shoot apical meristem under various environmental conditions, which cause adaptations in meristem size. Based on our results we developed a mathematical model to explain the observed changes by a cell pool size dependent regulation of cell proliferation and differentiation, which is able to correctly predict CLV3 and WUS over-expression phenotypes. While the model shows stem cell homeostasis under constant growth conditions, it predicts a variation in stem cell number under changing conditions. Consistent with our experimental data this behavior is correlated with variations in cell proliferation. Therefore, we investigate different signaling mechanisms, which could stabilize stem cell number despite variations in cell proliferation. Our results shed light onto the dynamic constraints of stem cell pool maintenance in the shoot apical meristem of Arabidopsis in different environmental conditions and developmental states.

  17. Evaluating sustainability of truck weight regulations: A system dynamics view

    Directory of Open Access Journals (Sweden)

    Pei Liu

    2015-11-01

    Full Text Available Purpose: Targeting the problem of overload trucking in Highway Transportation of iron ore from Caofeidian to Tangshan (HTCT, this paper aims to assess long-term effects of alternative Truck Weight Regulation (TWR policies on sustainability of HTCT. Design/methodology/approach: A system dynamics model was established for policy evaluation. The model, composed of six interrelating modules, is able to simulate policies effects on trucking issues such as freight flow, truck traffic flow, pavement performance, highway transport capacity and trucking time, and further on the Cumulative Economic Cost (CEC including transport cost and time cost of freight owners and the Cumulative Social Cost (CSC including pavement maintenance cost, green house gas emission cost, air pollutants emission cost and traffic accidents cost, so the effects of TWR policies on sustainability of HTCT could be evaluated. Findings: According to different values of overload ratio which a TWR policy allows, alternative TWR policies are classified into three types, which are The Rigid Policy (TRP, The Moderate Policy (TMP and The Tolerant Policy (TTP. Results show that the best policy for sustainability of HTCT depends on the importance of CSC which is expected by the local government. To be specific, (1 if CSC is considered much less important than CEC, the local government should continue implementing the current TTP with the maximum overload ratio; (2 if CSC is considered much more important than CEC, then TRP is recommended; and (3 if CSC is considered slightly more important than CES, TMP with overload ratio of 80% is the best. Practical implications: Conclusions of this paper may help the local government design appropriate TWR policies to achieve sustainability of HTCT. Originality/value: To the best of our knowledge, this is the first effort to evaluate TWR policies on sustainability of regional freight transportation based on system dynamics modeling.

  18. Dynamic regulation of Drosophila nuclear receptor activity in vivo.

    Science.gov (United States)

    Palanker, Laura; Necakov, Aleksandar S; Sampson, Heidi M; Ni, Ruoyu; Hu, Chun; Thummel, Carl S; Krause, Henry M

    2006-09-01

    Nuclear receptors are a large family of transcription factors that play major roles in development, metamorphosis, metabolism and disease. To determine how, where and when nuclear receptors are regulated by small chemical ligands and/or protein partners, we have used a 'ligand sensor' system to visualize spatial activity patterns for each of the 18 Drosophila nuclear receptors in live developing animals. Transgenic lines were established that express the ligand binding domain of each nuclear receptor fused to the DNA-binding domain of yeast GAL4. When combined with a GAL4-responsive reporter gene, the fusion proteins show tissue- and stage-specific patterns of activation. We show that these responses accurately reflect the presence of endogenous and exogenously added hormone, and that they can be modulated by nuclear receptor partner proteins. The amnioserosa, yolk, midgut and fat body, which play major roles in lipid storage, metabolism and developmental timing, were identified as frequent sites of nuclear receptor activity. We also see dynamic changes in activation that are indicative of sweeping changes in ligand and/or co-factor production. The screening of a small compound library using this system identified the angular psoralen angelicin and the insect growth regulator fenoxycarb as activators of the Ultraspiracle (USP) ligand-binding domain. These results demonstrate the utility of this system for the functional dissection of nuclear receptor pathways and for the development of new receptor agonists and antagonists that can be used to modulate metabolism and disease and to develop more effective means of insect control.

  19. A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC) system.

    Science.gov (United States)

    Sudomoina, Marina; Latypova, Ekaterina; Favorova, Olga O; Golemis, Erica A; Serebriiskii, Ilya G

    2004-04-29

    Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC) system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

  20. A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC system

    Directory of Open Access Journals (Sweden)

    Golemis Erica A

    2004-04-01

    Full Text Available Abstract Background Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. Results In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. Conclusion This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

  1. Multiple Scale Analysis of the Dynamic State Index (DSI)

    Science.gov (United States)

    Müller, A.; Névir, P.

    2016-12-01

    The Dynamic State Index (DSI) is a novel parameter that indicates local deviations of the atmospheric flow field from a stationary, inviscid and adiabatic solution of the primitive equations of fluid mechanics. This is in contrast to classical methods, which often diagnose deviations from temporal or spatial mean states. We show some applications of the DSI to atmospheric flow phenomena on different scales. The DSI is derived from the Energy-Vorticity-Theory (EVT) which is based on two global conserved quantities, the total energy and Ertel's potential enstrophy. Locally, these global quantities lead to the Bernoulli function and the PV building together with the potential temperature the DSI.If the Bernoulli function and the PV are balanced, the DSI vanishes and the basic state is obtained. Deviations from the basic state provide an indication of diabatic and non-stationary weather events. Therefore, the DSI offers a tool to diagnose and even prognose different atmospheric events on different scales.On synoptic scale, the DSI can help to diagnose storms and hurricanes, where also the dipole structure of the DSI plays an important role. In the scope of the collaborative research center "Scaling Cascades in Complex Systems" we show high correlations between the DSI and precipitation on convective scale. Moreover, we compare the results with reduced models and different spatial resolutions.

  2. Early Seizure Detection Based on Cardiac Autonomic Regulation Dynamics

    Directory of Open Access Journals (Sweden)

    Jonatas Pavei

    2017-10-01

    Full Text Available Epilepsy is a neurological disorder that causes changes in the autonomic nervous system. Heart rate variability (HRV reflects the regulation of cardiac activity and autonomic nervous system tone. The early detection of epileptic seizures could foster the use of new treatment approaches. This study presents a new methodology for the prediction of epileptic seizures using HRV signals. Eigendecomposition of HRV parameter covariance matrices was used to create an input for a support vector machine (SVM-based classifier. We analyzed clinical data from 12 patients (9 female; 3 male; age 34.5 ± 7.5 years, involving 34 seizures and a total of 55.2 h of interictal electrocardiogram (ECG recordings. Data from 123.6 h of ECG recordings from healthy subjects were used to test false positive rate per hour (FP/h in a completely independent data set. Our methodological approach allowed the detection of impending seizures from 5 min to just before the onset of a clinical/electrical seizure with a sensitivity of 94.1%. The FP rate was 0.49 h−1 in the recordings from patients with epilepsy and 0.19 h−1 in the recordings from healthy subjects. Our results suggest that it is feasible to use the dynamics of HRV parameters for the early detection and, potentially, the prediction of epileptic seizures.

  3. Nuclear Regulator Knowledge Management in a Dynamic Nuclear Industry Environment

    International Nuclear Information System (INIS)

    Turner, J.

    2016-01-01

    Full text: The paper outlines the experiences to date in developing mature knowledge management within the UK’s nuclear regulatory body The Office for Nuclear Regulation (ONR). In 2010 concerns over the loss of knowledge due to the age profile within the organization instigated a review of knowledge management and the development of a knowledge management initiative. Initially activities focused on knowledge capture but in order to move to through life knowledge transfer, knowledge management was then aligned with organizational resilience initiatives. A review of progress highlighted the need to better engage the whole organization to achieve the desired level of maturity for knowledge management. Knowledge management activities now cover organizational culture and environment and all aspects of organizational resilience. Benefits to date include clear understanding of core knowledge requirements, better specifications for recruitment and training and the ability to deploy new regulatory approaches. During the period of implementing the knowledge management programme ONR undertook several organizational changes in moving to become a separate statutory body. The UK nuclear industry was in a period of increased activity including the planning of new nuclear reactors. This dynamic environment caused challenges for embedding knowledge management within ONR which are discussed in the paper. (author

  4. Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.

    Directory of Open Access Journals (Sweden)

    Xiaoke Ma

    2015-06-01

    Full Text Available Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules. We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.

  5. Molecular kinetics. Ras activation by SOS: allosteric regulation by altered fluctuation dynamics.

    Science.gov (United States)

    Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen; Christensen, Sune M; Abel, Steven M; Iwig, Jeff; Wu, Hung-Jen; Gureasko, Jodi; Rhodes, Christopher; Petit, Rebecca S; Hansen, Scott D; Thill, Peter; Yu, Cheng-Han; Stamou, Dimitrios; Chakraborty, Arup K; Kuriyan, John; Groves, Jay T

    2014-07-04

    Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras-guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average. Copyright © 2014, American Association for the Advancement of Science.

  6. Emotion regulation and the dynamics of feelings: A conceptual and methodological framework [IF: 3.3

    NARCIS (Netherlands)

    Hoeksma, J.B.; Oosterlaan, J.; Schipper, E.M.

    2004-01-01

    The emotional system is defined as a dynamical system that has neurological and biochemical structures that force the system to change in a regular and consistent way. This dynamic view allows for an alternative definition of emotion regulation, which describes when emotion regulation is needed,

  7. Emotion Regulation and the Dynamics of Feelings: A Conceptual and Methodological Framework

    Science.gov (United States)

    Hoeksma, Jan B.; Oosterlaan, Jaap; Schipper, Eline M.

    2004-01-01

    The emotional system is defined as a dynamical system that has neurological and biochemical structures that force the system to change in a regular and consistent way. This dynamic view allows for an alternative definition of emotion regulation, which describes when emotion regulation is needed, identifies its goal, and illustrates how regulation…

  8. Emotion regulation and the dynamic of feelings: A conceptual and methodological framework

    NARCIS (Netherlands)

    Hoeksma, J.B.; Oosterlaan, J.; Schipper, E.

    2004-01-01

    The emotional system is defined as a dynamical system that has neurological and biochemical structures that force the system to change in a regular and consistent way. This dynamic view allows for an alternative definition of emotion regulation, which describes when emotion regulation is needed,

  9. TLR Stimulation Dynamically Regulates Heme and Iron Export Gene Expression in Macrophages

    Directory of Open Access Journals (Sweden)

    Mary Philip

    2016-01-01

    Full Text Available Pathogenic bacteria have evolved multiple mechanisms to capture iron or iron-containing heme from host tissues or blood. In response, organisms have developed defense mechanisms to keep iron from pathogens. Very little of the body’s iron store is available as free heme; rather nearly all body iron is complexed with heme or other proteins. The feline leukemia virus, subgroup C (FeLV-C receptor, FLVCR, exports heme from cells. It was unknown whether FLVCR regulates heme-iron availability after infection, but given that other heme regulatory proteins are upregulated in macrophages in response to bacterial infection, we hypothesized that macrophages dynamically regulate FLVCR. We stimulated murine primary macrophages or macrophage cell lines with LPS and found that Flvcr is rapidly downregulated in a TLR4/MD2-dependent manner; TLR1/2 and TLR3 stimulation also decreased Flvcr expression. We identified several candidate TLR-activated transcription factors that can bind to the Flvcr promoter. Macrophages must balance the need to sequester iron from systemic circulating or intracellular pathogens with the macrophage requirement for heme and iron to produce reactive oxygen species. Our findings underscore the complexity of this regulation and point to a new role for FLVCR and heme export in macrophages responses to infection and inflammation.

  10. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

    Science.gov (United States)

    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

  11. The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts

    Directory of Open Access Journals (Sweden)

    Perry Trinity L

    2007-11-01

    Full Text Available Abstract Background Heparan sulfate proteoglycans modulate signaling by a variety of growth factors. The mammalian proteoglycan Perlecan binds and regulates signaling by Sonic Hedgehog, Fibroblast Growth Factors (FGFs, Vascular Endothelial Growth Factor (VEGF and Platelet Derived Growth Factor (PDGF, among others, in contexts ranging from angiogenesis and cardiovascular development to cancer progression. The Drosophila Perlecan homolog trol has been shown to regulate the activity of Hedgehog and Branchless (an FGF homolog to control the onset of stem cell proliferation in the developing brain during first instar. Here we extend analysis of trol mutant phenotypes to show that trol is required for a variety of developmental events and modulates signaling by multiple growth factors in different situations. Results Different mutations in trol allow developmental progression to varying extents, suggesting that trol is involved in multiple cell-fate and patterning decisions. Analysis of the initiation of neuroblast proliferation at second instar demonstrated that trol regulates this event by modulating signaling by Hedgehog and Branchless, as it does during first instar. Trol protein is distributed over the surface of the larval brain, near the regulated neuroblasts that reside on the cortical surface. Mutations in trol also decrease the number of circulating plasmatocytes. This is likely to be due to decreased expression of pointed, the response gene for VEGF/PDGF signaling that is required for plasmatocyte proliferation. Trol is found on plasmatocytes, where it could regulate VEGF/PDGF signaling. Finally, we show that in second instar brains but not third instar brain lobes and eye discs, mutations in trol affect signaling by Decapentaplegic (a Transforming Growth Factor family member, Wingless (a Wnt growth factor and Hedgehog. Conclusion These studies extend the known functions of the Drosophila Perlecan homolog trol in both developmental and

  12. A quasi-sequential parameter estimation for nonlinear dynamic systems based on multiple data profiles

    International Nuclear Information System (INIS)

    Zhao, Chao; Vu, Quoc Dong; Li, Pu

    2013-01-01

    A three-stage computation framework for solving parameter estimation problems for dynamic systems with multiple data profiles is developed. The dynamic parameter estimation problem is transformed into a nonlinear programming (NLP) problem by using collocation on finite elements. The model parameters to be estimated are treated in the upper stage by solving an NLP problem. The middle stage consists of multiple NLP problems nested in the upper stage, representing the data reconciliation step for each data profile. We use the quasi-sequential dynamic optimization approach to solve these problems. In the lower stage, the state variables and their gradients are evaluated through ntegrating the model equations. Since the second-order derivatives are not required in the computation framework this proposed method will be efficient for solving nonlinear dynamic parameter estimation problems. The computational results obtained on a parameter estimation problem for two CSTR models demonstrate the effectiveness of the proposed approach

  13. A quasi-sequential parameter estimation for nonlinear dynamic systems based on multiple data profiles

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Chao [FuZhou University, FuZhou (China); Vu, Quoc Dong; Li, Pu [Ilmenau University of Technology, Ilmenau (Germany)

    2013-02-15

    A three-stage computation framework for solving parameter estimation problems for dynamic systems with multiple data profiles is developed. The dynamic parameter estimation problem is transformed into a nonlinear programming (NLP) problem by using collocation on finite elements. The model parameters to be estimated are treated in the upper stage by solving an NLP problem. The middle stage consists of multiple NLP problems nested in the upper stage, representing the data reconciliation step for each data profile. We use the quasi-sequential dynamic optimization approach to solve these problems. In the lower stage, the state variables and their gradients are evaluated through ntegrating the model equations. Since the second-order derivatives are not required in the computation framework this proposed method will be efficient for solving nonlinear dynamic parameter estimation problems. The computational results obtained on a parameter estimation problem for two CSTR models demonstrate the effectiveness of the proposed approach.

  14. Choline Catabolism in Burkholderia thailandensis Is Regulated by Multiple Glutamine Amidotransferase 1-Containing AraC Family Transcriptional Regulators.

    Science.gov (United States)

    Nock, Adam M; Wargo, Matthew J

    2016-09-15

    Burkholderia thailandensis is a soil-dwelling bacterium that shares many metabolic pathways with the ecologically similar, but evolutionarily distant, Pseudomonas aeruginosa Among the diverse nutrients it can utilize is choline, metabolizable to the osmoprotectant glycine betaine and subsequently catabolized as a source of carbon and nitrogen, similar to P. aeruginosa Orthologs of genes in the choline catabolic pathway in these two bacteria showed distinct differences in gene arrangement as well as an additional orthologous transcriptional regulator in B. thailandensis In this study, we showed that multiple glutamine amidotransferase 1 (GATase 1)-containing AraC family transcription regulators (GATRs) are involved in regulation of the B. thailandensis choline catabolic pathway (gbdR1, gbdR2, and souR). Using genetic analyses and sequencing the transcriptome in the presence and absence of choline, we identified the likely regulons of gbdR1 (BTH_II1869) and gbdR2 (BTH_II0968). We also identified a functional ortholog for P. aeruginosa souR, a GATR that regulates the metabolism of sarcosine to glycine. GbdR1 is absolutely required for expression of the choline catabolic locus, similar to P. aeruginosa GbdR, while GbdR2 is important to increase expression of the catabolic locus. Additionally, the B. thailandensis SouR ortholog (BTH_II0994) is required for catabolism of choline and its metabolites as carbon sources, whereas in P. aeruginosa, SouR function can by bypassed by GbdR. The strategy employed by B. thailandensis represents a distinct regulatory solution to control choline catabolism and thus provides both an evolutionary counterpoint and an experimental system to analyze the acquisition and regulation of this pathway during environmental growth and infection. Many proteobacteria that occupy similar environmental niches have horizontally acquired orthologous genes for metabolism of compounds useful in their shared environment. The arrangement and differential

  15. Endocytosis of collagen by hepatic stellate cells regulates extracellular matrix dynamics.

    Science.gov (United States)

    Bi, Yan; Mukhopadhyay, Dhriti; Drinane, Mary; Ji, Baoan; Li, Xing; Cao, Sheng; Shah, Vijay H

    2014-10-01

    Hepatic stellate cells (HSCs) generate matrix, which in turn may also regulate HSCs function during liver fibrosis. We hypothesized that HSCs may endocytose matrix proteins to sense and respond to changes in microenvironment. Primary human HSCs, LX2, or mouse embryonic fibroblasts (MEFs) [wild-type; c-abl(-/-); or Yes, Src, and Fyn knockout mice (YSF(-/-))] were incubated with fluorescent-labeled collagen or gelatin. Fluorescence-activated cell sorting analysis and confocal microscopy were used for measuring cellular internalization of matrix proteins. Targeted PCR array and quantitative real-time PCR were used to evaluate gene expression changes. HSCs and LX2 cells endocytose collagens in a concentration- and time-dependent manner. Endocytosed collagen colocalized with Dextran 10K, a marker of macropinocytosis, and 5-ethylisopropyl amiloride, an inhibitor of macropinocytosis, reduced collagen internalization by 46%. Cytochalasin D and ML7 blocked collagen internalization by 47% and 45%, respectively, indicating that actin and myosin are critical for collagen endocytosis. Wortmannin and AKT inhibitor blocked collagen internalization by 70% and 89%, respectively, indicating that matrix macropinocytosis requires phosphoinositide-3-kinase (PI3K)/AKT signaling. Overexpression of dominant-negative dynamin-2 K44A blocked matrix internalization by 77%, indicating a role for dynamin-2 in matrix macropinocytosis. Whereas c-abl(-/-) MEF showed impaired matrix endocytosis, YSF(-/-) MEF surprisingly showed increased matrix endocytosis. It was also associated with complex gene regulations that related with matrix dynamics, including increased matrix metalloproteinase 9 (MMP-9) mRNA levels and zymographic activity. HSCs endocytose matrix proteins through macropinocytosis that requires a signaling network composed of PI3K/AKT, dynamin-2, and c-abl. Interaction with extracellular matrix regulates matrix dynamics through modulating multiple gene expressions including MMP-9

  16. Language Multiplicity and Dynamism: Emergent Bilinguals Taking Ownership of Language Use in a Hybrid Curricular Space

    Science.gov (United States)

    Martínez-Álvarez, Patricia

    2017-01-01

    This study explores the impact of hybrid instructional spaces on the purposeful and expansive use of translanguaging practices. Utilizing technology, the study explores the role of multimodality in bilinguals' language multiplicity and dynamism. The research addresses: (a) how do emergent bilinguals in dual language programs deploy their full…

  17. Moral motivation based on multiple developmental structures: an exploration of cognitive and emotional dynamics.

    Science.gov (United States)

    Kaplan, Ulas; Tivnan, Terrence

    2014-01-01

    Intrapersonal variability and multiplicity in the complexity of moral motivation were examined from Dynamic Systems and Self-Determination Theory perspectives. L. Kohlberg's (1969) stages of moral development are reconceptualized as soft-assembled and dynamically transformable process structures of motivation that may operate simultaneously within person in different degrees. Moral motivation is conceptualized as the real-time process of self-organization of cognitive and emotional dynamics out of which moral judgment and action emerge. A detailed inquiry into intrapersonal variation in moral motivation is carried out based on the differential operation of multiple motivational structures. A total of 74 high school students and 97 college students participated in the study by completing a new questionnaire, involving 3 different hypothetical moral judgments. As hypothesized, findings revealed significant multiplicity in the within-person operation of developmental stage structures, and intrapersonal variability in the degrees to which stages were used. Developmental patterns were found in terms of different distributions of multiple stages between high school and college samples, as well as the association between age and overall motivation scores. Differential relations of specific emotions to moral motivation revealed and confirmed the value of differentiating multiple emotions. Implications of the present theoretical perspective and the findings for understanding the complexity of moral judgment and motivation are discussed.

  18. Analysis of Dynamic Behavior of Multiple-Stage Planetary Gear Train Used in Wind Driven Generator

    Directory of Open Access Journals (Sweden)

    Jungang Wang

    2014-01-01

    Full Text Available A dynamic model of multiple-stage planetary gear train composed of a two-stage planetary gear train and a one-stage parallel axis gear is proposed to be used in wind driven generator to analyze the influence of revolution speed and mesh error on dynamic load sharing characteristic based on the lumped parameter theory. Dynamic equation of the model is solved using numerical method to analyze the uniform load distribution of the system. It is shown that the load sharing property of the system is significantly affected by mesh error and rotational speed; load sharing coefficient and change rate of internal and external meshing of the system are of obvious difference from each other. The study provides useful theoretical guideline for the design of the multiple-stage planetary gear train of wind driven generator.

  19. Application of multiple tabu search algorithm to solve dynamic economic dispatch considering generator constraints

    International Nuclear Information System (INIS)

    Pothiya, Saravuth; Ngamroo, Issarachai; Kongprawechnon, Waree

    2008-01-01

    This paper presents a new optimization technique based on a multiple tabu search algorithm (MTS) to solve the dynamic economic dispatch (ED) problem with generator constraints. In the constrained dynamic ED problem, the load demand and spinning reserve capacity as well as some practical operation constraints of generators, such as ramp rate limits and prohibited operating zone are taken into consideration. The MTS algorithm introduces additional mechanisms such as initialization, adaptive searches, multiple searches, crossover and restarting process. To show its efficiency, the MTS algorithm is applied to solve constrained dynamic ED problems of power systems with 6 and 15 units. The results obtained from the MTS algorithm are compared to those achieved from the conventional approaches, such as simulated annealing (SA), genetic algorithm (GA), tabu search (TS) algorithm and particle swarm optimization (PSO). The experimental results show that the proposed MTS algorithm approaches is able to obtain higher quality solutions efficiently and with less computational time than the conventional approaches

  20. Robust set-point regulation for ecological models with multiple management goals.

    Science.gov (United States)

    Guiver, Chris; Mueller, Markus; Hodgson, Dave; Townley, Stuart

    2016-05-01

    Population managers will often have to deal with problems of meeting multiple goals, for example, keeping at specific levels both the total population and population abundances in given stage-classes of a stratified population. In control engineering, such set-point regulation problems are commonly tackled using multi-input, multi-output proportional and integral (PI) feedback controllers. Building on our recent results for population management with single goals, we develop a PI control approach in a context of multi-objective population management. We show that robust set-point regulation is achieved by using a modified PI controller with saturation and anti-windup elements, both described in the paper, and illustrate the theory with examples. Our results apply more generally to linear control systems with positive state variables, including a class of infinite-dimensional systems, and thus have broader appeal.

  1. Addressing the regulatory and scientific challenges in multiple sclerosis--a statement from the EU regulators.

    Science.gov (United States)

    Balabanov, Pavel; Haas, Manuel; Elferink, Andre; Bakchine, Serge; Broich, Karl

    2014-09-01

    Improving and facilitating the process of making new drugs available to patients with multiple sclerosis (MS) requires cooperation among the regulators and other stakeholders. This cooperation will also positively contribute towards developing guidelines of the highest quality in medical, regulatory and scientific aspects. This would be beneficial both in areas that require further guideline development, but also in fields where existing guidance should be adapted to take into account evolution in science. Considering the input from all stakeholders, the European Medicines Agency confirmed its intention to update the relevant guideline and apply a flexible approach towards new drug development strategies in MS. This article is the first official position from the EU regulators, presenting the main changes to be expected in the guidance document. © The Author(s) 2014.

  2. IVF policy and global/local politics: the making of multiple-embryo transfer regulation in Taiwan.

    Science.gov (United States)

    Wu, Chia-Ling

    2012-08-01

    This paper analyzes the regulatory trajectory of multiple-embryo transfer in in-vitro fertilization (IVF) in Taiwan. Taking a latecomer to policy-making as the case, it argues the importance of conceptualizing the global/local dynamics in policy-making for assisted reproductive technology (ART). The conceptual framework is built upon recent literature on standardization, science policy, and global assemblage. I propose three interrelated features that reveal the "global in the local": (1) the power relationships among stakeholders, (2) the selected global form that involved actors drew upon, and (3) the re-contextualized assemblage made of local networks. Data included archives, interviews, and participant observation. In different historical periods the specific stakeholders selected different preferred global forms for Taiwan, such as Britain's code of ethics in the 1990s, the American guideline in the early 2000s, and the European trend in the mid-2000s. The global is heterogeneous. The failure to transfer the British regulation, the revision of the American guideline by adding one more embryo than it specified, and the gap between the cited European trend and the "no more than four" in Taiwan's 2007 Human Reproduction Law all show that the local network further transforms the selected global form, confining it to rhetoric only or tailoring it to local needs. Overall, Taiwanese practitioners successfully maintained their medical autonomy to build a 'flexible standardization'. Multiple pregnancy remains the most common health risk of IVF in Taiwan. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Multiple layers of posttranslational regulation refine circadian clock activity in Arabidopsis.

    Science.gov (United States)

    Seo, Pil Joon; Mas, Paloma

    2014-01-01

    The circadian clock is a cellular time-keeper mechanism that regulates biological rhythms with a period of ~24 h. The circadian rhythms in metabolism, physiology, and development are synchronized by environmental cues such as light and temperature. In plants, proper matching of the internal circadian time with the external environment confers fitness advantages on plant survival and propagation. Accordingly, plants have evolved elaborated regulatory mechanisms that precisely control the circadian oscillations. Transcriptional feedback regulation of several clock components has been well characterized over the past years. However, the importance of additional regulatory mechanisms such as chromatin remodeling, protein complexes, protein phosphorylation, and stability is only starting to emerge. The multiple layers of circadian regulation enable plants to properly synchronize with the environmental cycles and to fine-tune the circadian oscillations. This review focuses on the diverse posttranslational events that regulate circadian clock function. We discuss the mechanistic insights explaining how plants articulate a high degree of complexity in their regulatory networks to maintain circadian homeostasis and to generate highly precise waveforms of circadian expression and activity.

  4. Optimal Route Searching with Multiple Dynamical Constraints—A Geometric Algebra Approach

    Directory of Open Access Journals (Sweden)

    Dongshuang Li

    2018-05-01

    Full Text Available The process of searching for a dynamic constrained optimal path has received increasing attention in traffic planning, evacuation, and personalized or collaborative traffic service. As most existing multiple constrained optimal path (MCOP methods cannot search for a path given various types of constraints that dynamically change during the search, few approaches for dynamic multiple constrained optimal path (DMCOP with type II dynamics are available for practical use. In this study, we develop a method to solve the DMCOP problem with type II dynamics based on the unification of various types of constraints under a geometric algebra (GA framework. In our method, the network topology and three different types of constraints are represented by using algebraic base coding. With a parameterized optimization of the MCOP algorithm based on a greedy search strategy under the generation-refinement paradigm, this algorithm is found to accurately support the discovery of optimal paths as the constraints of numerical values, nodes, and route structure types are dynamically added to the network. The algorithm was tested with simulated cases of optimal tourism route searches in China’s road networks with various combinations of constraints. The case study indicates that our algorithm can not only solve the DMCOP with different types of constraints but also use constraints to speed up the route filtering.

  5. Frequency Splitting Elimination and Cross-Coupling Rejection of Wireless Power Transfer to Multiple Dynamic Receivers

    Directory of Open Access Journals (Sweden)

    Narayanamoorthi R.

    2018-01-01

    Full Text Available Simultaneous power transfer to multiple receiver (Rx system is one of the key advantages of wireless power transfer (WPT system using magnetic resonance. However, determining the optimal condition to uniformly transfer the power to a selected Rx at high efficiency is the challenging task under the dynamic environment. The cross-coupling and frequency splitting are the dominant issues present in the multiple Rx dynamic WPT system. The existing analysis is performed by considering any one issue present in the system; on the other hand, the cross coupling and frequency splitting issues are interrelated in dynamic Rx’s, which requires a comprehensive design strategy by considering both the problems. This paper proposes an optimal design of multiple Rx WPT system, which can eliminate cross coupling, frequency splitting issues and increase the power transfer efficiency (PTE of selected Rx. The cross-coupling rejection, uniform power transfer is performed by adding an additional relay coil and independent resonance frequency tuning with capacitive compensation to each Rx unit. The frequency splitting phenomena are eliminated using non-identical transmitter (Tx and Rx coil structure which can maintain the coupling between the coil under the critical coupling limit. The mathematical analysis of the compensation capacitance calculation and optimal Tx coil size identification is performed for the four Rx WPT system. Finite element analysis and experimental investigation are carried out for the proposed design in static and dynamic conditions.

  6. Dynamic Bus Travel Time Prediction Models on Road with Multiple Bus Routes

    Science.gov (United States)

    Bai, Cong; Peng, Zhong-Ren; Lu, Qing-Chang; Sun, Jian

    2015-01-01

    Accurate and real-time travel time information for buses can help passengers better plan their trips and minimize waiting times. A dynamic travel time prediction model for buses addressing the cases on road with multiple bus routes is proposed in this paper, based on support vector machines (SVMs) and Kalman filtering-based algorithm. In the proposed model, the well-trained SVM model predicts the baseline bus travel times from the historical bus trip data; the Kalman filtering-based dynamic algorithm can adjust bus travel times with the latest bus operation information and the estimated baseline travel times. The performance of the proposed dynamic model is validated with the real-world data on road with multiple bus routes in Shenzhen, China. The results show that the proposed dynamic model is feasible and applicable for bus travel time prediction and has the best prediction performance among all the five models proposed in the study in terms of prediction accuracy on road with multiple bus routes. PMID:26294903

  7. Dynamic Bus Travel Time Prediction Models on Road with Multiple Bus Routes.

    Science.gov (United States)

    Bai, Cong; Peng, Zhong-Ren; Lu, Qing-Chang; Sun, Jian

    2015-01-01

    Accurate and real-time travel time information for buses can help passengers better plan their trips and minimize waiting times. A dynamic travel time prediction model for buses addressing the cases on road with multiple bus routes is proposed in this paper, based on support vector machines (SVMs) and Kalman filtering-based algorithm. In the proposed model, the well-trained SVM model predicts the baseline bus travel times from the historical bus trip data; the Kalman filtering-based dynamic algorithm can adjust bus travel times with the latest bus operation information and the estimated baseline travel times. The performance of the proposed dynamic model is validated with the real-world data on road with multiple bus routes in Shenzhen, China. The results show that the proposed dynamic model is feasible and applicable for bus travel time prediction and has the best prediction performance among all the five models proposed in the study in terms of prediction accuracy on road with multiple bus routes.

  8. ANGUSTIFOLIA mediates one of the multiple SCRAMBLED signaling pathways regulating cell growth pattern in Arabidopsis thaliana.

    Science.gov (United States)

    Kwak, Su-Hwan; Song, Sang-Kee; Lee, Myeong Min; Schiefelbein, John

    2015-09-25

    In Arabidopsis thaliana, an atypical leucine-rich repeat receptor-like kinase, SCRAMBLED (SCM), is required for multiple developmental processes including root epidermal cell fate determination, silique dehiscence, inflorescence growth, ovule morphogenesis, and tissue morphology. Previous work suggested that SCM regulates these multiple pathways using distinct mechanisms via interactions with specific downstream factors. ANGUSTIFOLIA (AN) is known to regulate cell and tissue morphogenesis by influencing cortical microtubule arrangement, and recently, the AN protein was reported to interact with the SCM protein. Therefore, we examined whether AN might be responsible for mediating some of the SCM-dependent phenotypes. We discovered that both scm and an mutant lines cause an abnormal spiral or twisting growth of roots, but only the scm mutant affected root epidermal patterning. The siliques of the an and scm mutants also exhibited spiral growth, as previously reported, but only the scm mutant altered silique dehiscence. Interestingly, we discovered that the spiral growth of roots and siliques of the scm mutant is rescued by a truncated SCM protein that lacks its kinase domain, and that a juxtamembrane domain of SCM was sufficient for AN binding in the yeast two-hybrid analysis. These results suggest that the AN protein is one of the critical downstream factors of SCM pathways specifically responsible for mediating its effects on cell/tissue morphogenesis through cortical microtubule arrangement. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development.

    Science.gov (United States)

    Lentucci, Claudia; Belkina, Anna C; Cederquist, Carly T; Chan, Michelle; Johnson, Holly E; Prasad, Sherry; Lopacinski, Amanda; Nikolajczyk, Barbara S; Monti, Stefano; Snyder-Cappione, Jennifer; Tanasa, Bogdan; Cardamone, M Dafne; Perissi, Valentina

    2017-02-17

    Non-proteolytic ubiquitin signaling mediated by Lys 63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNFα signaling and lipid metabolism in the adipose tissue through modulation of Lys 63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Stress and serial adult metamorphosis: Multiple roles for the stress axis in socially regulated sex change

    Directory of Open Access Journals (Sweden)

    Tessa K Solomon-Lane

    2013-11-01

    Full Text Available Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis. Through actions of both corticotropin-releasing factor and glucocorticoids (GCs, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli, a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

  11. Stress and serial adult metamorphosis: multiple roles for the stress axis in socially regulated sex change.

    Science.gov (United States)

    Solomon-Lane, Tessa K; Crespi, Erica J; Grober, Matthew S

    2013-01-01

    Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis). Through actions of both corticotropin-releasing factor and glucocorticoids, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli), a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

  12. The multiple time scales of sleep dynamics as a challenge for modelling the sleeping brain.

    Science.gov (United States)

    Olbrich, Eckehard; Claussen, Jens Christian; Achermann, Peter

    2011-10-13

    A particular property of the sleeping brain is that it exhibits dynamics on very different time scales ranging from the typical sleep oscillations such as sleep spindles and slow waves that can be observed in electroencephalogram (EEG) segments of several seconds duration over the transitions between the different sleep stages on a time scale of minutes to the dynamical processes involved in sleep regulation with typical time constants in the range of hours. There is an increasing body of work on mathematical and computational models addressing these different dynamics, however, usually considering only processes on a single time scale. In this paper, we review and present a new analysis of the dynamics of human sleep EEG at the different time scales and relate the findings to recent modelling efforts pointing out both the achievements and remaining challenges.

  13. Multiple coupled landscapes and non-adiabatic dynamics with applications to self-activating genes.

    Science.gov (United States)

    Chen, Cong; Zhang, Kun; Feng, Haidong; Sasai, Masaki; Wang, Jin

    2015-11-21

    Many physical, chemical and biochemical systems (e.g. electronic dynamics and gene regulatory networks) are governed by continuous stochastic processes (e.g. electron dynamics on a particular electronic energy surface and protein (gene product) synthesis) coupled with discrete processes (e.g. hopping among different electronic energy surfaces and on and off switching of genes). One can also think of the underlying dynamics as the continuous motion on a particular landscape and discrete hoppings among different landscapes. The main difference of such systems from the intra-landscape dynamics alone is the emergence of the timescale involved in transitions among different landscapes in addition to the timescale involved in a particular landscape. The adiabatic limit when inter-landscape hoppings are fast compared to continuous intra-landscape dynamics has been studied both analytically and numerically, but the analytical treatment of the non-adiabatic regime where the inter-landscape hoppings are slow or comparable to continuous intra-landscape dynamics remains challenging. In this study, we show that there exists mathematical mapping of the dynamics on 2(N) discretely coupled N continuous dimensional landscapes onto one single landscape in 2N dimensional extended continuous space. On this 2N dimensional landscape, eddy current emerges as a sign of non-equilibrium non-adiabatic dynamics and plays an important role in system evolution. Many interesting physical effects such as the enhancement of fluctuations, irreversibility, dissipation and optimal kinetics emerge due to non-adiabaticity manifested by the eddy current illustrated for an N = 1 self-activator. We further generalize our theory to the N-gene network with multiple binding sites and multiple synthesis rates for discretely coupled non-equilibrium stochastic physical and biological systems.

  14. Regulation of hTERT by BCR-ABL at multiple levels in K562 cells

    International Nuclear Information System (INIS)

    Chai, Juin Hsien; Zhang, Yong; Tan, Wei Han; Chng, Wee Joo; Li, Baojie; Wang, Xueying

    2011-01-01

    The cytogenetic characteristic of Chronic Myeloid Leukemia (CML) is the formation of the Philadelphia chromosome gene product, BCR-ABL. Given that BCR-ABL is the specific target of Gleevec in CML treatment, we investigated the regulation of the catalytic component of telomerase, hTERT, by BCR-ABL at multiple levels in K562 cells. Molecular techniques such as over expression, knockdown, real-time PCR, immunoprecipitation, western blotting, reporter assay, confocal microscopy, telomerase assays and microarray were used to suggest that hTERT expression and activity is modulated by BCR-ABL at multiple levels. Our results suggest that BCR-ABL plays an important role in regulating hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec inhibited the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was downregulated, therefore suggesting a positive correlation between BCR-ABL and hTERT. Gleevec treatment inhibited hTERT at mRNA level and significantly reduced telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells (BCR-ABL negative cells). We also demonstrated that the transcription factor STAT5a plays a critical role in hTERT gene regulation in K562 cells. Knockdown of STAT5a, but not STAT5b, resulted in a marked downregulation of hTERT mRNA level, TA and hTERT protein level in K562 cells. Furthermore, translocation of hTERT from nucleoli to nucleoplasm was observed in K562 cells induced by Gleevec. Our data reveal that BCR-ABL can regulate TA at multiple levels, including transcription, post-translational level, and proper localization. Thus, suppression of cell growth and induction of apoptosis by Gleevec treatment may be partially due to TA inhibition. Additionally, we have identified STAT5a as critical mediator of the hTERT gene expression in BCR-ABL positive CML cells, suggesting that targeting STAT5a may be a promising therapeutic strategy for BCR-ABL positive CML patients

  15. Low-frequency dynamics of autonomic regulation of circulatory system in healthy subjects

    Science.gov (United States)

    Skazkina, V. V.; Borovkova, E. I.; Galushko, T. A.; Khorev, V. S.; Kiselev, A. R.

    2018-04-01

    The paper is devoted to the analysis of dynamic of interactions between signals of autonomic circulatory regulation. We investigated two-hour experimental records of 30 healthy people. Phase synchronization was studied using the signals of the electrocardiogram and the photoplethysmogram of vessels. We found the presence of long synchronous intervals in some subjects. For analysis of the dynamic we calculated autocorrelation functions. The analysis made it possible to reveal indirect signs of the influence of the humoral regulation system.

  16. Free Energy Reconstruction from Logarithmic Mean-Force Dynamics Using Multiple Nonequilibrium Trajectories.

    Science.gov (United States)

    Morishita, Tetsuya; Yonezawa, Yasushige; Ito, Atsushi M

    2017-07-11

    Efficient and reliable estimation of the mean force (MF), the derivatives of the free energy with respect to a set of collective variables (CVs), has been a challenging problem because free energy differences are often computed by integrating the MF. Among various methods for computing free energy differences, logarithmic mean-force dynamics (LogMFD) [ Morishita et al., Phys. Rev. E 2012 , 85 , 066702 ] invokes the conservation law in classical mechanics to integrate the MF, which allows us to estimate the free energy profile along the CVs on-the-fly. Here, we present a method called parallel dynamics, which improves the estimation of the MF by employing multiple replicas of the system and is straightforwardly incorporated in LogMFD or a related method. In the parallel dynamics, the MF is evaluated by a nonequilibrium path-ensemble using the multiple replicas based on the Crooks-Jarzynski nonequilibrium work relation. Thanks to the Crooks relation, realizing full-equilibrium states is no longer mandatory for estimating the MF. Additionally, sampling in the hidden subspace orthogonal to the CV space is highly improved with appropriate weights for each metastable state (if any), which is hardly achievable by typical free energy computational methods. We illustrate how to implement parallel dynamics by combining it with LogMFD, which we call logarithmic parallel dynamics (LogPD). Biosystems of alanine dipeptide and adenylate kinase in explicit water are employed as benchmark systems to which LogPD is applied to demonstrate the effect of multiple replicas on the accuracy and efficiency in estimating the free energy profiles using parallel dynamics.

  17. Effect of Food Regulation on the Spanish Food Processing Industry: A Dynamic Productivity Analysis.

    Science.gov (United States)

    Kapelko, Magdalena; Oude Lansink, Alfons; Stefanou, Spiro E

    2015-01-01

    This article develops the decomposition of the dynamic Luenberger productivity growth indicator into dynamic technical change, dynamic technical inefficiency change and dynamic scale inefficiency change in the dynamic directional distance function context using Data Envelopment Analysis. These results are used to investigate for the Spanish food processing industry the extent to which dynamic productivity growth and its components are affected by the introduction of the General Food Law in 2002 (Regulation (EC) No 178/2002). The empirical application uses panel data of Spanish meat, dairy, and oils and fats industries over the period 1996-2011. The results suggest that in the oils and fats industry the impact of food regulation on dynamic productivity growth is negative initially and then positive over the long run. In contrast, the opposite pattern is observed for the meat and dairy processing industries. The results further imply that firms in the meat processing and oils and fats industries face similar impacts of food safety regulation on dynamic technical change, dynamic inefficiency change and dynamic scale inefficiency change.

  18. Effect of Food Regulation on the Spanish Food Processing Industry: A Dynamic Productivity Analysis

    Science.gov (United States)

    Kapelko, Magdalena; Lansink, Alfons Oude; Stefanou, Spiro E.

    2015-01-01

    This article develops the decomposition of the dynamic Luenberger productivity growth indicator into dynamic technical change, dynamic technical inefficiency change and dynamic scale inefficiency change in the dynamic directional distance function context using Data Envelopment Analysis. These results are used to investigate for the Spanish food processing industry the extent to which dynamic productivity growth and its components are affected by the introduction of the General Food Law in 2002 (Regulation (EC) No 178/2002). The empirical application uses panel data of Spanish meat, dairy, and oils and fats industries over the period 1996-2011. The results suggest that in the oils and fats industry the impact of food regulation on dynamic productivity growth is negative initially and then positive over the long run. In contrast, the opposite pattern is observed for the meat and dairy processing industries. The results further imply that firms in the meat processing and oils and fats industries face similar impacts of food safety regulation on dynamic technical change, dynamic inefficiency change and dynamic scale inefficiency change. PMID:26057878

  19. Regulation of the syncytin-1 promoter in human astrocytes by multiple sclerosis-related cytokines

    International Nuclear Information System (INIS)

    Mameli, Giuseppe; Astone, Vito; Khalili, Kamel; Serra, Caterina; Sawaya, Bassel E.; Dolei, Antonina

    2007-01-01

    Syncytin-1 has a physiological role during early pregnancy, as mediator of trophoblast fusion into the syncytiotrophoblast layer, hence allowing embryo implantation. In addition, its expression in nerve tissue has been proposed to contribute to the pathogenesis of multiple sclerosis (MS). Syncytin-1 is the env glycoprotein of the ERVWE1 component of the W family of human endogenous retroviruses (HERV), located on chromosome 7q21-22, in a candidate region for genetic susceptibility to MS. The mechanisms of ERVWE1 regulation in nerve tissue remain to be identified. Since there are correlations between some cytokines and MS outcome, we examined the regulation of the syncytin-1 promoter by MS-related cytokines in human U-87MG astrocytic cells. Using transient transfection assays, we observed that the MS-detrimental cytokines TNFα, interferon-γ, interleukin-6, and interleukin-1 activate the ERVWE1 promoter, while the MS-protective interferon-β is inhibitory. The effects of cytokines are reduced by the deletion of the cellular enhancer domain of the promoter that contains binding sites for several transcription factors. In particular, we found that TNFα had the ability to activate the ERVWE1 promoter through an NF-κB-responsive element located within the enhancer domain of the promoter. Electrophoretic mobility shift and ChIP assays showed that TNFα enhances the binding of the p65 subunit of NF-κB, to its cognate site within the promoter. The effect of TNFα is abolished by siRNA directed against p65. Taken together, these results illustrate a role for p65 in regulating the ERVWE1 promoter and in TNFα-mediated induction of syncytin-1 in multiple sclerosis

  20. C/EBPβ Mediates Growth Hormone-Regulated Expression of Multiple Target Genes

    Science.gov (United States)

    Cui, Tracy X.; Lin, Grace; LaPensee, Christopher R.; Calinescu, Anda-Alexandra; Rathore, Maanjot; Streeter, Cale; Piwien-Pilipuk, Graciela; Lanning, Nathan; Jin, Hui; Carter-Su, Christin; Qin, Zhaohui S.

    2011-01-01

    Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBPβ led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBPβ mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBPβ at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBPβ and p300 on Cyr61, Btg2, and Socs3 at predicted C/EBP-cAMP response element-binding protein motifs in their promoters. Consistent with a role for ERKs in GH-induced expression of these genes, treatment with U0126 to block ERK phosphorylation inhibited their GH-induced expression. In contrast, GH-dependent expression of Zfp36 and Socs1 was not inhibited by U0126. Thus, induction of multiple early response genes by GH in 3T3-F442A cells is mediated by C/EBPβ. A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPβ, and recruitment of p300. Overall, these studies suggest that C/EBPβ, like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH. PMID:21292824

  1. Inferring Ice Thickness from a Glacier Dynamics Model and Multiple Surface Datasets.

    Science.gov (United States)

    Guan, Y.; Haran, M.; Pollard, D.

    2017-12-01

    The future behavior of the West Antarctic Ice Sheet (WAIS) may have a major impact on future climate. For instance, ice sheet melt may contribute significantly to global sea level rise. Understanding the current state of WAIS is therefore of great interest. WAIS is drained by fast-flowing glaciers which are major contributors to ice loss. Hence, understanding the stability and dynamics of glaciers is critical for predicting the future of the ice sheet. Glacier dynamics are driven by the interplay between the topography, temperature and basal conditions beneath the ice. A glacier dynamics model describes the interactions between these processes. We develop a hierarchical Bayesian model that integrates multiple ice sheet surface data sets with a glacier dynamics model. Our approach allows us to (1) infer important parameters describing the glacier dynamics, (2) learn about ice sheet thickness, and (3) account for errors in the observations and the model. Because we have relatively dense and accurate ice thickness data from the Thwaites Glacier in West Antarctica, we use these data to validate the proposed approach. The long-term goal of this work is to have a general model that may be used to study multiple glaciers in the Antarctic.

  2. Priority and Negotiation Based Dynamic Spectrum Allocation Scheme for Multiple Radio Access Network Operators

    Science.gov (United States)

    Kim, Hoon; Hyon, Taein; Lee, Yeonwoo

    Most of previous works have presented the dynamic spectrum allocation (DSA) gain achieved by utilizing the time or regional variations in traffic demand between multi-network operators (NOs). In this paper, we introduce the functionalities required for the entities related with the spectrum sharing and allocation and propose a spectrum allocation algorithm while considering the long-term priority between NOs, the priority between multiple class services, and the urgent bandwidth request. To take into account the priorities among the NOs and the priorities of multiple class services, a spectrum sharing metric (SSM) is proposed, while a negotiation procedure is proposed to treat the urgent bandwidth request.

  3. DYNAMIC ANALYSIS OF A CRIMPING DEVICE WITH MULTIPLE CAMS USING MSC ADAMS II

    Directory of Open Access Journals (Sweden)

    Gheorghe Popescu

    2012-05-01

    Full Text Available Through the present paper, the author presents the results of the dynamic analysis with MSC ADAMS of the mechanism with a crimping device with 12 tightening cams, designed and used in the technological process of assembly of the indigenous electrical detonators. In this sense, the mechanism with multiple cams is considered a mechanical system and is treated as an assembly of rigid bodies connected by mechanical connections and elastic elements. For shaping and simulation of the mechanism with multiple cams using ADAMS program, the author got through the following stages: construction of the pattern, its testing and simulation, validation, finishing, parametrization, optimization of the pattern.

  4. Dynamics and regulation at the tip : a high resolution view on microtubele assembly

    NARCIS (Netherlands)

    Munteanu, Laura

    2008-01-01

    Microtubules are highly dynamic protein polymers that and are essential for intracellular organization and fundamental processes like transport and cell division. In cells, a wide family of microtubule-associated proteins (MAPs) tightly regulates microtubule dynamics. The work presented in this

  5. Confinement and dynamical regulation in two-dimensional convective turbulence

    DEFF Research Database (Denmark)

    Bian, N.H.; Garcia, O.E.

    2003-01-01

    In this work the nature of confinement improvement implied by the self-consistent generation of mean flows in two-dimensional convective turbulence is studied. The confinement variations are linked to two distinct regulation mechanisms which are also shown to be at the origin of low......-frequency bursting in the fluctuation level and the convective heat flux integral, both resulting in a state of large-scale intermittency. The first one involves the control of convective transport by sheared mean flows. This regulation relies on the conservative transfer of kinetic energy from tilted fluctuations...

  6. NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin

    Directory of Open Access Journals (Sweden)

    Paula Schiapparelli

    2017-07-01

    Full Text Available Glioblastoma (GBM is the most aggressive primary brain tumor in adults. The mechanisms that confer GBM cells their invasive behavior are poorly understood. The electroneutral Na+-K+-2Cl− co-transporter 1 (NKCC1 is an important cell volume regulator that participates in cell migration. We have shown that inhibition of NKCC1 in GBM cells leads to decreased cell migration, in vitro and in vivo. We now report on the role of NKCC1 on cytoskeletal dynamics. We show that GBM cells display a significant decrease in F-actin content upon NKCC1 knockdown (NKCC1-KD. To determine the potential actin-regulatory mechanisms affected by NKCC1 inhibition, we studied NKCC1 protein interactions. We found that NKCC1 interacts with the actin-regulating protein Cofilin-1 and can regulate its membrane localization. Finally, we analyzed whether NKCC1 could regulate the activity of the small Rho-GTPases RhoA and Rac1. We observed that the active forms of RhoA and Rac1 were decreased in NKCC1-KD cells. In summary, we report that NKCC1 regulates GBM cell migration by modulating the cytoskeleton through multiple targets including F-actin regulation through Cofilin-1 and RhoGTPase activity. Due to its essential role in cell migration NKCC1 may serve as a specific therapeutic target to decrease cell invasion in patients with primary brain cancer.

  7. Fine tuning of RFX/DAF-19-regulated target gene expression through binding to multiple sites in Caenorhabditis elegans

    OpenAIRE

    Chu, Jeffery S. C.; Tarailo-Graovac, Maja; Zhang, Di; Wang, Jun; Uyar, Bora; Tu, Domena; Trinh, Joanne; Baillie, David L.; Chen, Nansheng

    2011-01-01

    In humans, mutations of a growing list of regulatory factor X (RFX) target genes have been associated with devastating genetics disease conditions including ciliopathies. However, mechanisms underlying RFX transcription factors (TFs)-mediated gene expression regulation, especially differential gene expression regulation, are largely unknown. In this study, we explore the functional significance of the co-existence of multiple X-box motifs in regulating differential gene expression in Caenorha...

  8. Mechanisms regulating regional cerebral activation during dynamic handgrip in humans

    DEFF Research Database (Denmark)

    Williamson, James; Friedman, D B; Mitchell, J H

    1996-01-01

    Dynamic hand movement increases regional cerebral blood flow (rCBF) of the contralateral motor sensory cortex (MS1). This increase is eliminated by regional anesthesia of the working arm, indicating the importance of afferent neural input. The purpose of this study was to determine the specific...

  9. Security Analysis of a Block Encryption Algorithm Based on Dynamic Sequences of Multiple Chaotic Systems

    Science.gov (United States)

    Du, Mao-Kang; He, Bo; Wang, Yong

    2011-01-01

    Recently, the cryptosystem based on chaos has attracted much attention. Wang and Yu (Commun. Nonlin. Sci. Numer. Simulat. 14 (2009) 574) proposed a block encryption algorithm based on dynamic sequences of multiple chaotic systems. We analyze the potential flaws in the algorithm. Then, a chosen-plaintext attack is presented. Some remedial measures are suggested to avoid the flaws effectively. Furthermore, an improved encryption algorithm is proposed to resist the attacks and to keep all the merits of the original cryptosystem.

  10. Differences in dynamic balance scores in one sport versus multiple sport high school athletes.

    Science.gov (United States)

    Gorman, Paul P; Butler, Robert J; Rauh, Mitchell J; Kiesel, Kyle; Plisky, Phillip J

    2012-04-01

    Researchers have previously reported on the importance of dynamic balance in assessing an individual's risk for injury during sport. However, to date there is no research on whether multiple sport participation affects dynamic balance ability. Therefore, the purpose of this study was to determine if there was a difference in dynamic balance scores in high school athletes that competed in one sport only as compared athletes who competed in multiple sports, as tested by the Lower Quarter Y Balance Test (YBT-LQ). Ninety-two high school athletes who participated in one sport were matched, by age, gender and sport played, to athletes who participated in the same sport as well as additional sports. All individuals were assessed using the YBT-LQ to examine differences in composite reach score and reach direction asymmetry between single sport and multiple sport athletes. The greatest reach distance of three trials in each reach direction for right and left lower-extremities was normalized by limb length and used for analysis. A two-way ANOVA (gender x number of sports played) was used to statistically analyze the variables in the study. No significant interactions or main effects related to number of sports played were observed for any YBT-LQ score (p>0.05). Male athletes exhibited significantly greater normalized reach values for the posteromedial, posterolateral, and composite reach while also exhibiting a larger anterior reach difference when compared to the females. Athletes who participated in multiple sports had similar performances on the YBT-LQ when compared to athletes who participated in a single sport. The findings of this study suggest that the number of sports played by a high school athlete does not need to be controlled for when evaluating dynamic balance with the YBT-LQ.

  11. A SCHEDULING SCHEME WITH DYNAMIC FREQUENCY CLOCKING AND MULTIPLE VOLTAGES FOR LOW POWER DESIGNS

    Institute of Scientific and Technical Information of China (English)

    Wen Dongxin; Wang Ling; Yang Xiaozong

    2007-01-01

    In this letter, a scheduling scheme based on Dynamic Frequency Clocking (DFC) and multiple voltages is proposed for low power designs under the timing and the resource constraints.Unlike the conventional methods at high level synthesis where only voltages of nodes were considered,the scheme based on a gain function considers both voltage and frequency simultaneously to reduce energy consumption. Experiments with a number of DSP benchmarks show that the proposed scheme achieves an effective energy reduction.

  12. Multiple attractors and dynamics in an OLG model with productive environment

    Science.gov (United States)

    Caravaggio, Andrea; Sodini, Mauro

    2018-05-01

    This work analyses an overlapping generations model in which economic activity depends on the exploitation of a free-access natural resource. In addition, public expenditures for environmental maintenance are assumed. By characterising some properties of the map and performing numerical simulations, we investigate consequences of the interplay between environmental public expenditure and private sector. In particular, we identify different scenarios in which multiple equilibria as well as complex dynamics may arise.

  13. Robust handling of dynamics and multiple failures in a diagnostic event analyzer

    International Nuclear Information System (INIS)

    Finch, F.E.; Kramer, M.A.

    1991-01-01

    MIDAS diagnoses malfunctions in continuous chemical and refinery processes using a plant-independent strategy based on qualitative and quantitative process models. MIDAS specifically addresses problems not treated in past systems, including: process dynamics with control system responses, multiple faults and induced failures, and out-of-order and false alarms. This paper discusses both the structure of the process models and the diagnostic reasoning strategies employed by MIDAS

  14. Quantum theory of dynamic multiple light scattering in fluctuating disordered media

    International Nuclear Information System (INIS)

    Skipetrov, S. E.

    2007-01-01

    We formulate a quantum theory of dynamic multiple light scattering in fluctuating disordered media and calculate the fluctuation and the autocorrelation function of the photon number operator for light transmitted through a disordered slab. The effect of disorder on the information capacity of a quantum communication channel operating in a disordered environment is estimated, and the use of squeezed light in diffusing-wave spectroscopy is discussed

  15. Endothelin-1 Regulation of exercise-induced changes in flow: Dynamic regulation of vascular tone

    NARCIS (Netherlands)

    Rapoport, R.M. (Robert M.); D. Merkus (Daphne)

    2017-01-01

    textabstractAlthough endothelin (ET)-1 is a highly potent vasoconstrictor with considerable efficacy in numerous vascular beds, the role of endogenous ET-1 in the regulation of vascular tone remains unclear. The perspective that ET-1 plays little role in the on-going regulation of vascular tone at

  16. Minimal agent based model for financial markets II. Statistical properties of the linear and multiplicative dynamics

    Science.gov (United States)

    Alfi, V.; Cristelli, M.; Pietronero, L.; Zaccaria, A.

    2009-02-01

    We present a detailed study of the statistical properties of the Agent Based Model introduced in paper I [Eur. Phys. J. B, DOI: 10.1140/epjb/e2009-00028-4] and of its generalization to the multiplicative dynamics. The aim of the model is to consider the minimal elements for the understanding of the origin of the stylized facts and their self-organization. The key elements are fundamentalist agents, chartist agents, herding dynamics and price behavior. The first two elements correspond to the competition between stability and instability tendencies in the market. The herding behavior governs the possibility of the agents to change strategy and it is a crucial element of this class of models. We consider a linear approximation for the price dynamics which permits a simple interpretation of the model dynamics and, for many properties, it is possible to derive analytical results. The generalized non linear dynamics results to be extremely more sensible to the parameter space and much more difficult to analyze and control. The main results for the nature and self-organization of the stylized facts are, however, very similar in the two cases. The main peculiarity of the non linear dynamics is an enhancement of the fluctuations and a more marked evidence of the stylized facts. We will also discuss some modifications of the model to introduce more realistic elements with respect to the real markets.

  17. Coupling dynamic analysis of spacecraft with multiple cylindrical tanks and flexible appendages

    Science.gov (United States)

    Wu, Wen-Jun; Yue, Bao-Zeng; Huang, Hua

    2016-02-01

    This paper is mainly concerned with the coupling dynamic analysis of a complex spacecraft consisting of one main rigid platform, multiple liquid-filled cylindrical tanks, and a number of flexible appendages. Firstly, the carrier potential function equations of liquid in the tanks are deduced according to the wall boundary conditions. Through employing the Fourier-Bessel series expansion method, the dynamic boundaries conditions on a curved free-surface under a low-gravity environment are transformed to general simple differential equations and the rigid-liquid coupled sloshing dynamic state equations of liquid in tanks are obtained. The state vectors of rigid-liquid coupled equations are composed with the modal coordinates of the relative potential function and the modal coordinates of wave height. Based on the Bernoulli-Euler beam theory and the D'Alembert's principle, the rigid-flexible coupled dynamic state equations of flexible appendages are directly derived, and the coordinate transform matrixes of maneuvering flexible appendages are precisely computed as time-varying. Then, the coupling dynamics state equations of the overall system of the spacecraft are modularly built by means of the Lagrange's equations in terms of quasi-coordinates. Lastly, the coupling dynamic performances of a typical complex spacecraft are studied. The availability and reliability of the presented method are also confirmed.

  18. A new multiple robot path planning algorithm: dynamic distributed particle swarm optimization.

    Science.gov (United States)

    Ayari, Asma; Bouamama, Sadok

    2017-01-01

    Multiple robot systems have become a major study concern in the field of robotic research. Their control becomes unreliable and even infeasible if the number of robots increases. In this paper, a new dynamic distributed particle swarm optimization (D 2 PSO) algorithm is proposed for trajectory path planning of multiple robots in order to find collision-free optimal path for each robot in the environment. The proposed approach consists in calculating two local optima detectors, LOD pBest and LOD gBest . Particles which are unable to improve their personal best and global best for predefined number of successive iterations would be replaced with restructured ones. Stagnation and local optima problems would be avoided by adding diversity to the population, without losing the fast convergence characteristic of PSO. Experiments with multiple robots are provided and proved effectiveness of such approach compared with the distributed PSO.

  19. Symbolic dynamics and synchronization of coupled map networks with multiple delays

    International Nuclear Information System (INIS)

    Atay, Fatihcan M.; Jalan, Sarika; Jost, Juergen

    2010-01-01

    We use symbolic dynamics to study discrete-time dynamical systems with multiple time delays. We exploit the concept of avoiding sets, which arise from specific non-generating partitions of the phase space and restrict the occurrence of certain symbol sequences related to the characteristics of the dynamics. In particular, we show that the resulting forbidden sequences are closely related to the time delays in the system. We present two applications to coupled map lattices, namely (1) detecting synchronization and (2) determining unknown values of the transmission delays in networks with possibly directed and weighted connections and measurement noise. The method is applicable to multi-dimensional as well as set-valued maps, and to networks with time-varying delays and connection structure.

  20. The Dynamics and Sliding Mode Control of Multiple Cooperative Welding Robot Manipulators

    Directory of Open Access Journals (Sweden)

    Bin Zi

    2012-08-01

    Full Text Available This paper deals with the design, dynamic modelling and sliding mode control of multiple cooperative welding robot manipulators (MWRMs. The MWRMs can handle complex tasks that are difficult or even impossible for a single manipulator. The kinematics and dynamics of the MWRMs are studied on the basis of the Denavit-Hartenberg and Lagrange method. Following that, considering the MWRM system with nonlinear and unknown disturbances, a non-singular terminal sliding mode control strategy is designed. By means of the Lyapunov function, the stability of the controller is proved. Simulation results indicate that the good control performance of the MWRMs is achieved by the non-singular terminal sliding mode controller, which also illustrates the correctness of the dynamic modelling and effectiveness of the proposed control strategy.

  1. Simulating Dynamic Stall Effects for Vertical Axis Wind Turbines Applying a Double Multiple Streamtube Model

    Directory of Open Access Journals (Sweden)

    Eduard Dyachuk

    2015-02-01

    Full Text Available The complex unsteady aerodynamics of vertical axis wind turbines (VAWT poses significant challenges to the simulation tools. Dynamic stall is one of the phenomena associated with the unsteady conditions for VAWTs, and it is in the focus of the study. Two dynamic stall models are compared: the widely-used Gormont model and a Leishman–Beddoes-type model. The models are included in a double multiple streamtube model. The effects of flow curvature and flow expansion are also considered. The model results are assessed against the measured data on a Darrieus turbine with curved blades. To study the dynamic stall effects, the comparison of force coefficients between the simulations and experiments is done at low tip speed ratios. Simulations show that the Leishman–Beddoes model outperforms the Gormont model for all tested conditions.

  2. A Neural Network Model to Learn Multiple Tasks under Dynamic Environments

    Science.gov (United States)

    Tsumori, Kenji; Ozawa, Seiichi

    When environments are dynamically changed for agents, the knowledge acquired in an environment might be useless in future. In such dynamic environments, agents should be able to not only acquire new knowledge but also modify old knowledge in learning. However, modifying all knowledge acquired before is not efficient because the knowledge once acquired may be useful again when similar environment reappears and some knowledge can be shared among different environments. To learn efficiently in such environments, we propose a neural network model that consists of the following modules: resource allocating network, long-term & short-term memory, and environment change detector. We evaluate the model under a class of dynamic environments where multiple function approximation tasks are sequentially given. The experimental results demonstrate that the proposed model possesses stable incremental learning, accurate environmental change detection, proper association and recall of old knowledge, and efficient knowledge transfer.

  3. Dynamic Nature of Noncoding RNA Regulation of Adaptive Immune Response

    Directory of Open Access Journals (Sweden)

    Franca Citarella

    2013-08-01

    Full Text Available Immune response plays a fundamental role in protecting the organism from infections; however, dysregulation often occurs and can be detrimental for the organism, leading to a variety of immune-mediated diseases. Recently our understanding of the molecular and cellular networks regulating the immune response, and, in particular, adaptive immunity, has improved dramatically. For many years, much of the focus has been on the study of protein regulators; nevertheless, recent evidence points to a fundamental role for specific classes of noncoding RNAs (ncRNAs in regulating development, activation and homeostasis of the immune system. Although microRNAs (miRNAs are the most comprehensive and well-studied, a number of reports suggest the exciting possibility that long ncRNAs (lncRNAs could mediate host response and immune function. Finally, evidence is also accumulating that suggests a role for miRNAs and other small ncRNAs in autocrine, paracrine and exocrine signaling events, thus highlighting an elaborate network of regulatory interactions mediated by different classes of ncRNAs during immune response. This review will explore the multifaceted roles of ncRNAs in the adaptive immune response. In particular, we will focus on the well-established role of miRNAs and on the emerging role of lncRNAs and circulating ncRNAs, which all make indispensable contributions to the understanding of the multilayered modulation of the adaptive immune response.

  4. Catecholaminergic Regulation of Learning Rate in a Dynamic Environment.

    Directory of Open Access Journals (Sweden)

    Marieke Jepma

    2016-10-01

    Full Text Available Adaptive behavior in a changing world requires flexibly adapting one's rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the 'learning rate'. However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32 that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG-an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex-predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables-capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief-on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants' baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change.

  5. Catecholaminergic Regulation of Learning Rate in a Dynamic Environment.

    Science.gov (United States)

    Jepma, Marieke; Murphy, Peter R; Nassar, Matthew R; Rangel-Gomez, Mauricio; Meeter, Martijn; Nieuwenhuis, Sander

    2016-10-01

    Adaptive behavior in a changing world requires flexibly adapting one's rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the 'learning rate'). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG-an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex-predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables-capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief-on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants' baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change.

  6. Progranulin acts as a shared chaperone and regulates multiple lysosomal enzymes

    Directory of Open Access Journals (Sweden)

    Jinlong Jian

    2017-09-01

    Full Text Available Multifunctional factor progranulin (PGRN plays an important role in lysosomes, and its mutations and insufficiency are associated with lysosomal storage diseases, including neuronal ceroid lipofuscinosis and Gaucher disease (GD. The first breakthrough in understanding the molecular mechanisms of PGRN as regulator of lysosomal storage diseases came unexpectedly while investigating the role of PGRN in inflammation. Challenged PGRN null mice displayed typical features of GD. In addition, GRN gene variants were identified in GD patients and the serum levels of PGRN were significantly lower in GD patients. PGRN directly binds to and functions as a chaperone of the lysosomal enzyme β-glucocerebrosidase (GCaase, whose mutations cause GD. In addition, its C-terminus containing granulin E domain, termed Pcgin (PGRN C-terminus for GCase Interaction, is required for the association between PGRN and GCase. The concept that PGRN acts as a chaperone of lysosomal enzymes was further supported and extended by a recent article showing that PGRN acts as a chaperone molecule of lysosomal enzyme cathepsin D (CSTD, and the association between PGRN and CSTD is also mediated by PGRN's C-terminal granulin E domain. Collectively, these reports suggest that PGRN may act as a shared chaperone and regulates multiple lysosomal enzymes.

  7. Trafficking of plant plasma membrane aquaporins: multiple regulation levels and complex sorting signals.

    Science.gov (United States)

    Chevalier, Adrien S; Chaumont, François

    2015-05-01

    Aquaporins are small channel proteins which facilitate the diffusion of water and small neutral molecules across biological membranes. Compared with animals, plant genomes encode numerous aquaporins, which display a large variety of subcellular localization patterns. More specifically, plant aquaporins of the plasma membrane intrinsic protein (PIP) subfamily were first described as plasma membrane (PM)-resident proteins, but recent research has demonstrated that the trafficking and subcellular localization of these proteins are complex and highly regulated. In the past few years, PIPs emerged as new model proteins to study subcellular sorting and membrane dynamics in plant cells. At least two distinct sorting motifs (one cytosolic, the other buried in the membrane) are required to direct PIPs to the PM. Hetero-oligomerization and interaction with SNAREs (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptors) also influence the subcellular trafficking of PIPs. In addition to these constitutive processes, both the progression of PIPs through the secretory pathway and their dynamics at the PM are responsive to changing environmental conditions. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. Reduced α-stable dynamics for multiple time scale systems forced with correlated additive and multiplicative Gaussian white noise

    Science.gov (United States)

    Thompson, William F.; Kuske, Rachel A.; Monahan, Adam H.

    2017-11-01

    Stochastic averaging problems with Gaussian forcing have been the subject of numerous studies, but far less attention has been paid to problems with infinite-variance stochastic forcing, such as an α-stable noise process. It has been shown that simple linear systems driven by correlated additive and multiplicative (CAM) Gaussian noise, which emerge in the context of reduced atmosphere and ocean dynamics, have infinite variance in certain parameter regimes. In this study, we consider the stochastic averaging of systems where a linear CAM noise process in the infinite variance parameter regime drives a comparatively slow process. We use (semi)-analytical approximations combined with numerical illustrations to compare the averaged process to one that is forced by a white α-stable process, demonstrating consistent properties in the case of large time-scale separation. We identify the conditions required for the fast linear CAM process to have such an influence in driving a slower process and then derive an (effectively) equivalent fast, infinite-variance process for which an existing stochastic averaging approximation is readily applied. The results are illustrated using numerical simulations of a set of example systems.

  9. Increased dynamic regulation of postural tone through Alexander Technique training.

    Science.gov (United States)

    Cacciatore, T W; Gurfinkel, V S; Horak, F B; Cordo, P J; Ames, K E

    2011-02-01

    Gurfinkel and colleagues (2006) recently found that healthy adults dynamically modulate postural muscle tone in the body axis during anti-gravity postural maintenance and that this modulation is inversely correlated with axial stiffness. Our objective in the present study was to investigate whether dynamic modulation of axial postural tone can change through training. We examined whether teachers of the Alexander Technique (AT), who undergo "long-term" (3-year) training, have greater modulation of axial postural tone than matched control subjects. In addition, we performed a longitudinal study on the effect of "short-term" (10-week) AT training on the axial postural tone of individuals with low back pain (LBP), since short term AT training has previously been shown to reduce LBP. Axial postural tone was quantified by measuring the resistance of the neck, trunk and hips to small (±10°), slow (1°/s) torsional rotation during stance. Modulation of tone was determined by the torsional resistance to rotation (peak-to-peak, phase-advance, and variability of torque) and axial muscle activity (EMG). Peak-to-peak torque was lower (∼50%), while phase-advance and cycle-to-cycle variability were enhanced for AT teachers compared to matched control subjects at all levels of the axis. In addition, LBP subjects decreased trunk and hip stiffness following short-term AT training compared to a control intervention. While changes in static levels of postural tone may have contributed to the reduced stiffness observed with the AT, our results suggest that dynamic modulation of postural tone can be enhanced through long-term training in the AT, which may constitute an important direction for therapeutic intervention. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Multiple oxygen tension environments reveal diverse patterns of transcriptional regulation in primary astrocytes.

    Directory of Open Access Journals (Sweden)

    Wayne Chadwick

    Full Text Available The central nervous system normally functions at O(2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O(2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O(2 tensions compared to the cell culture standard of 20% O(2, to investigate their ability to sense and translate this O(2 information to transcriptional activity. Variance of ambient O(2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O(2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O(2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O(2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional 'programs' may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity.

  11. Dynamic model of gene regulation for the lac operon

    Energy Technology Data Exchange (ETDEWEB)

    Angelova, Maia; Ben-Halim, Asma, E-mail: maia.angelova@northumbria.ac.uk, E-mail: asma.benhalim@northumbria.ac.uk [Intelligent Modelling Lab, School of Computing, Engineering and Information Sciences, Northumbria University, Newcastle upon Tyne NE2 1XE (United Kingdom)

    2011-03-01

    Gene regulatory network is a collection of DNA which interact with each other and with other matter in the cell. The lac operon is an example of a relatively simple genetic network and is one of the best-studied structures in the Escherichia coli bacteria. In this work we consider a deterministic model of the lac operon with a noise term, representing the stochastic nature of the regulation. The model is written in terms of a system of simultaneous first order differential equations with delays. We investigate an analytical and numerical solution and analyse the range of values for the parameters corresponding to a stable solution.

  12. Dynamic model of gene regulation for the lac operon

    International Nuclear Information System (INIS)

    Angelova, Maia; Ben-Halim, Asma

    2011-01-01

    Gene regulatory network is a collection of DNA which interact with each other and with other matter in the cell. The lac operon is an example of a relatively simple genetic network and is one of the best-studied structures in the Escherichia coli bacteria. In this work we consider a deterministic model of the lac operon with a noise term, representing the stochastic nature of the regulation. The model is written in terms of a system of simultaneous first order differential equations with delays. We investigate an analytical and numerical solution and analyse the range of values for the parameters corresponding to a stable solution.

  13. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development

    Science.gov (United States)

    Nissim, Sahar; Weeks, Olivia; Talbot, Jared C.; Hedgepeth, John W.; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E.; Amacher, Sharon L.; Goessling, Wolfram

    2016-01-01

    The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic versus pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. PMID:27474396

  14. ARCHITECTURE AND DYNAMICS OF KEPLER'S CANDIDATE MULTIPLE TRANSITING PLANET SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    Lissauer, Jack J.; Jenkins, Jon M.; Borucki, William J.; Bryson, Stephen T.; Howell, Steve B. [NASA Ames Research Center, Moffett Field, CA 94035 (United States); Ragozzine, Darin; Holman, Matthew J.; Carter, Joshua A. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Fabrycky, Daniel C.; Fortney, Jonathan J. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Steffen, Jason H. [Fermilab Center for Particle Astrophysics, Batavia, IL 60510 (United States); Ford, Eric B. [211 Bryant Space Science Center, University of Florida, Gainesville, FL 32611 (United States); Shporer, Avi [Las Cumbres Observatory Global Telescope Network, Santa Barbara, CA 93117 (United States); Rowe, Jason F.; Quintana, Elisa V.; Caldwell, Douglas A. [SETI Institute/NASA Ames Research Center, Moffett Field, CA 94035 (United States); Batalha, Natalie M. [Department of Physics and Astronomy, San Jose State University, San Jose, CA 95192 (United States); Ciardi, David [Exoplanet Science Institute/Caltech, Pasadena, CA 91125 (United States); Dunham, Edward W. [Lowell Observatory, Flagstaff, AZ 86001 (United States); Gautier, Thomas N. III, E-mail: Jack.Lissauer@nasa.gov [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); and others

    2011-11-01

    About one-third of the {approx}1200 transiting planet candidates detected in the first four months of Kepler data are members of multiple candidate systems. There are 115 target stars with two candidate transiting planets, 45 with three, 8 with four, and 1 each with five and six. We characterize the dynamical properties of these candidate multi-planet systems. The distribution of observed period ratios shows that the vast majority of candidate pairs are neither in nor near low-order mean-motion resonances. Nonetheless, there are small but statistically significant excesses of candidate pairs both in resonance and spaced slightly too far apart to be in resonance, particularly near the 2:1 resonance. We find that virtually all candidate systems are stable, as tested by numerical integrations that assume a nominal mass-radius relationship. Several considerations strongly suggest that the vast majority of these multi-candidate systems are true planetary systems. Using the observed multiplicity frequencies, we find that a single population of planetary systems that matches the higher multiplicities underpredicts the number of singly transiting systems. We provide constraints on the true multiplicity and mutual inclination distribution of the multi-candidate systems, revealing a population of systems with multiple super-Earth-size and Neptune-size planets with low to moderate mutual inclinations.

  15. Analysis of Dynamic Performance of a Kalman Filter for Combining Multiple MEMS Gyroscopes

    Directory of Open Access Journals (Sweden)

    Liang Xue

    2014-11-01

    Full Text Available In this paper, the dynamic performance of a Kalman filter (KF was analyzed, which is used to combine multiple measurements of a gyroscopes array to reduce the noise and improve the accuracy of the individual sensors. A principle for accuracy improvement by the KF was briefly presented to obtain an optimal estimate of input rate signal. In particular, the influences of some crucial factors on the KF dynamic performance were analyzed by simulations such as the factors input signal frequency, signal sampling, and KF filtering rate. Finally, a system that was comprised of a six-gyroscope array was designed and implemented to test the dynamic performance. Experimental results indicated that the 1σ error for the combined rate signal was reduced to about 0.2°/s in the constant rate test, which was a reduction by a factor of more than eight compared to the single gyroscope. The 1σ error was also reduced from 1.6°/s to 0.48°/s in the swing test. It showed that the estimated angular rate signal could well reflect the dynamic characteristic of the input signal in dynamic conditions.

  16. High Dynamic Velocity Range Particle Image Velocimetry Using Multiple Pulse Separation Imaging

    Directory of Open Access Journals (Sweden)

    Tadhg S. O’Donovan

    2010-12-01

    Full Text Available The dynamic velocity range of particle image velocimetry (PIV is determined by the maximum and minimum resolvable particle displacement. Various techniques have extended the dynamic range, however flows with a wide velocity range (e.g., impinging jets still challenge PIV algorithms. A new technique is presented to increase the dynamic velocity range by over an order of magnitude. The multiple pulse separation (MPS technique (i records series of double-frame exposures with different pulse separations, (ii processes the fields using conventional multi-grid algorithms, and (iii yields a composite velocity field with a locally optimized pulse separation. A robust criterion determines the local optimum pulse separation, accounting for correlation strength and measurement uncertainty. Validation experiments are performed in an impinging jet flow, using laser-Doppler velocimetry as reference measurement. The precision of mean flow and turbulence quantities is significantly improved compared to conventional PIV, due to the increase in dynamic range. In a wide range of applications, MPS PIV is a robust approach to increase the dynamic velocity range without restricting the vector evaluation methods.

  17. High dynamic velocity range particle image velocimetry using multiple pulse separation imaging.

    Science.gov (United States)

    Persoons, Tim; O'Donovan, Tadhg S

    2011-01-01

    The dynamic velocity range of particle image velocimetry (PIV) is determined by the maximum and minimum resolvable particle displacement. Various techniques have extended the dynamic range, however flows with a wide velocity range (e.g., impinging jets) still challenge PIV algorithms. A new technique is presented to increase the dynamic velocity range by over an order of magnitude. The multiple pulse separation (MPS) technique (i) records series of double-frame exposures with different pulse separations, (ii) processes the fields using conventional multi-grid algorithms, and (iii) yields a composite velocity field with a locally optimized pulse separation. A robust criterion determines the local optimum pulse separation, accounting for correlation strength and measurement uncertainty. Validation experiments are performed in an impinging jet flow, using laser-Doppler velocimetry as reference measurement. The precision of mean flow and turbulence quantities is significantly improved compared to conventional PIV, due to the increase in dynamic range. In a wide range of applications, MPS PIV is a robust approach to increase the dynamic velocity range without restricting the vector evaluation methods.

  18. Relationship between cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers: Exploring multiple mediation model.

    Science.gov (United States)

    Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui

    2017-10-01

    The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Multiple Time-Step Dual-Hamiltonian Hybrid Molecular Dynamics - Monte Carlo Canonical Propagation Algorithm.

    Science.gov (United States)

    Chen, Yunjie; Kale, Seyit; Weare, Jonathan; Dinner, Aaron R; Roux, Benoît

    2016-04-12

    A multiple time-step integrator based on a dual Hamiltonian and a hybrid method combining molecular dynamics (MD) and Monte Carlo (MC) is proposed to sample systems in the canonical ensemble. The Dual Hamiltonian Multiple Time-Step (DHMTS) algorithm is based on two similar Hamiltonians: a computationally expensive one that serves as a reference and a computationally inexpensive one to which the workload is shifted. The central assumption is that the difference between the two Hamiltonians is slowly varying. Earlier work has shown that such dual Hamiltonian multiple time-step schemes effectively precondition nonlinear differential equations for dynamics by reformulating them into a recursive root finding problem that can be solved by propagating a correction term through an internal loop, analogous to RESPA. Of special interest in the present context, a hybrid MD-MC version of the DHMTS algorithm is introduced to enforce detailed balance via a Metropolis acceptance criterion and ensure consistency with the Boltzmann distribution. The Metropolis criterion suppresses the discretization errors normally associated with the propagation according to the computationally inexpensive Hamiltonian, treating the discretization error as an external work. Illustrative tests are carried out to demonstrate the effectiveness of the method.

  20. Dynamic control of biped locomotion robot using optimal regulator

    International Nuclear Information System (INIS)

    Sano, Akihito; Furusho, Junji

    1988-01-01

    For moving in indoor space, it is generally recognized that biped locomotion is suitable. This paper proposes a hierarchical control strategy for the lower level where the position control or the force control at each joint is implemented. In the upper level control, the robot motion is divided into a sagittal plane and a lateral plane. We applied the optimal control algorithm to the motion control in the lateral plane in order to improve the robustness of the control system. The effects of these control schemes are shown by the experiments using the new walking robot BLR-G 1 and the parallel calculation system. BLR-G 1 has 9 degrees of freedom and equips the foot-pressure-sensors and a rate gyroscope. Complete dynamic walking is realized, in which the cycle for each step is about 1.0 second. (author)

  1. Dynamical Processes in Ageing, Gene Regulation and Communication

    DEFF Research Database (Denmark)

    Bendtsen, Kristian Moss

    is that unstable activation and stable repression is a requirement for the motif to produce oscillations. The last part of this thesis studies the emergence of communication networks. In this study we constructed a simple e-mail game. E-mails from two session with 16 players, who had never met before, showed how......My thesis consists of three parts. The first part covers ageing phenomena. In the first project I measured the mobility of two DNA repair proteins. Contrasting diffusion coefficients from literature I was able to classify DNA repair protein into either "scanners" or "responders". In a second...... project we constructed a mathematical model and showed that if DNA damage is primarily caused by geno-toxic agents, it would be advantageous for cells to have a fragile DNA repair mechanism. The second part of my Ph.D. thesis covers gene regulation. In the first project we show how RNA polymerase can...

  2. Characterization of microcirculation in multiple sclerosis lesions by dynamic texture parameter analysis (DTPA.

    Directory of Open Access Journals (Sweden)

    Rajeev Kumar Verma

    Full Text Available OBJECTIVE: Texture analysis is an alternative method to quantitatively assess MR-images. In this study, we introduce dynamic texture parameter analysis (DTPA, a novel technique to investigate the temporal evolution of texture parameters using dynamic susceptibility contrast enhanced (DSCE imaging. Here, we aim to introduce the method and its application on enhancing lesions (EL, non-enhancing lesions (NEL and normal appearing white matter (NAWM in multiple sclerosis (MS. METHODS: We investigated 18 patients with MS and clinical isolated syndrome (CIS, according to the 2010 McDonald's criteria using DSCE imaging at different field strengths (1.5 and 3 Tesla. Tissues of interest (TOIs were defined within 27 EL, 29 NEL and 37 NAWM areas after normalization and eight histogram-based texture parameter maps (TPMs were computed. TPMs quantify the heterogeneity of the TOI. For every TOI, the average, variance, skewness, kurtosis and variance-of-the-variance statistical parameters were calculated. These TOI parameters were further analyzed using one-way ANOVA followed by multiple Wilcoxon sum rank testing corrected for multiple comparisons. RESULTS: Tissue- and time-dependent differences were observed in the dynamics of computed texture parameters. Sixteen parameters discriminated between EL, NEL and NAWM (pAVG = 0.0005. Significant differences in the DTPA texture maps were found during inflow (52 parameters, outflow (40 parameters and reperfusion (62 parameters. The strongest discriminators among the TPMs were observed in the variance-related parameters, while skewness and kurtosis TPMs were in general less sensitive to detect differences between the tissues. CONCLUSION: DTPA of DSCE image time series revealed characteristic time responses for ELs, NELs and NAWM. This may be further used for a refined quantitative grading of MS lesions during their evolution from acute to chronic state. DTPA discriminates lesions beyond features of enhancement or T2

  3. Robustness analysis of uncertain dynamical neural networks with multiple time delays.

    Science.gov (United States)

    Senan, Sibel

    2015-10-01

    This paper studies the problem of global robust asymptotic stability of the equilibrium point for the class of dynamical neural networks with multiple time delays with respect to the class of slope-bounded activation functions and in the presence of the uncertainties of system parameters of the considered neural network model. By using an appropriate Lyapunov functional and exploiting the properties of the homeomorphism mapping theorem, we derive a new sufficient condition for the existence, uniqueness and global robust asymptotic stability of the equilibrium point for the class of neural networks with multiple time delays. The obtained stability condition basically relies on testing some relationships imposed on the interconnection matrices of the neural system, which can be easily verified by using some certain properties of matrices. An instructive numerical example is also given to illustrate the applicability of our result and show the advantages of this new condition over the previously reported corresponding results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Force regulated dynamics of RPA on a DNA fork.

    Science.gov (United States)

    Kemmerich, Felix E; Daldrop, Peter; Pinto, Cosimo; Levikova, Maryna; Cejka, Petr; Seidel, Ralf

    2016-07-08

    Replication protein A (RPA) is a single-stranded DNA binding protein, involved in most aspects of eukaryotic DNA metabolism. Here, we study the behavior of RPA on a DNA substrate that mimics a replication fork. Using magnetic tweezers we show that both yeast and human RPA can open forked DNA when sufficient external tension is applied. In contrast, at low force, RPA becomes rapidly displaced by the rehybridization of the DNA fork. This process appears to be governed by the binding or the release of an RPA microdomain (toehold) of only few base-pairs length. This gives rise to an extremely rapid exchange dynamics of RPA at the fork. Fork rezipping rates reach up to hundreds of base-pairs per second, being orders of magnitude faster than RPA dissociation from ssDNA alone. Additionally, we show that RPA undergoes diffusive motion on ssDNA, such that it can be pushed over long distances by a rezipping fork. Generally the behavior of both human and yeast RPA homologs is very similar. However, in contrast to yeast RPA, the dissociation of human RPA from ssDNA is greatly reduced at low Mg(2+) concentrations, such that human RPA can melt DNA in absence of force. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells.

    Science.gov (United States)

    Rymut, Sharon M; Kampman, Claire M; Corey, Deborah A; Endres, Tori; Cotton, Calvin U; Kelley, Thomas J

    2016-08-01

    High-dose ibuprofen, an effective anti-inflammatory therapy for the treatment of cystic fibrosis (CF), has been shown to preserve lung function in a pediatric population. Despite its efficacy, few patients receive ibuprofen treatment due to potential renal and gastrointestinal toxicity. The mechanism of ibuprofen efficacy is also unclear. We have previously demonstrated that CF microtubules are slower to reform after depolymerization compared with respective wild-type controls. Slower microtubule dynamics in CF cells are responsible for impaired intracellular transport and are related to inflammatory signaling. Here, it is identified that high-dose ibuprofen treatment in both CF cell models and primary CF nasal epithelial cells restores microtubule reformation rates to wild-type levels, as well as induce extension of microtubules to the cell periphery. Ibuprofen treatment also restores microtubule-dependent intracellular transport monitored by measuring intracellular cholesterol transport. These effects are specific to ibuprofen as other cyclooxygenase inhibitors have no effect on these measures. Effects of ibuprofen are mimicked by stimulation of AMPK and blocked by the AMPK inhibitor compound C. We conclude that high-dose ibuprofen treatment enhances microtubule formation in CF cells likely through an AMPK-related pathway. These findings define a potential mechanism to explain the efficacy of ibuprofen therapy in CF. Copyright © 2016 the American Physiological Society.

  6. Renal blood flow regulation and arterial pressure fluctuations: a case study in nonlinear dynamics

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Marsh, D J

    1994-01-01

    in which the kidney is obliged to operate. Were it not for renal blood flow autoregulation, it would be difficult to regulate renal excretory processes so as to maintain whole body variables within narrow bounds. Autoregulation is the noise filter on which other renal processes depend for maintaining...... a relatively noise-free environment in which to work. Because of the time-varying nature of the blood pressure, we have concentrated in this review on the now substantial body of work on the dynamics of renal blood flow regulation and the underlying mechanisms. Renal vascular control mechanisms are not simply....... The significance of deterministic chaos in the context of renal blood flow regulation is that the system regulating blood flow undergoes a physical change to a different dynamical state, and because the change is deterministic, there is every expectation that the critical change will yield itself to experimental...

  7. Solving the Single-Sink, Fixed-Charge, Multiple-Choice Transportation Problem by Dynamic Programming

    DEFF Research Database (Denmark)

    Christensen, Tue; Andersen, Kim Allan; Klose, Andreas

    2013-01-01

    This paper considers a minimum-cost network flow problem in a bipartite graph with a single sink. The transportation costs exhibit a staircase cost structure because such types of transportation cost functions are often found in practice. We present a dynamic programming algorithm for solving...... this so-called single-sink, fixed-charge, multiple-choice transportation problem exactly. The method exploits heuristics and lower bounds to peg binary variables, improve bounds on flow variables, and reduce the state-space variable. In this way, the dynamic programming method is able to solve large...... instances with up to 10,000 nodes and 10 different transportation modes in a few seconds, much less time than required by a widely used mixed-integer programming solver and other methods proposed in the literature for this problem....

  8. Dynamics of quantum Fisher information in a two-level system coupled to multiple bosonic reservoirs

    Science.gov (United States)

    Wang, Guo-You; Guo, You-Neng; Zeng, Ke

    2015-11-01

    We consider the optimal parameter estimation for a two-level system coupled to multiple bosonic reservoirs. By using quantum Fisher information (QFI), we investigate the effect of the Markovian reservoirs’ number N on QFI in both weak and strong coupling regimes for a two-level system surrounded by N zero-temperature reservoirs of field modes initially in the vacua. The results show that the dynamics of QFI non-monotonically decays to zero with revival oscillations at some time in the weak coupling regime depending on the reservoirs’ parameters. Furthermore, we also present the relations between the QFI flow, the flows of energy and information, and the sign of the decay rate to gain insight into the physical processes characterizing the dynamics. Project supported by the Hunan Provincial Innovation Foundation for Postgraduate, China (Grant No. CX2014B194) and the Scientific Research Foundation of Hunan Provincial Education Department, China (Grant No. 13C039).

  9. Identifying the Micro-relations Underpinning Familiarity Detection in Dynamic Displays Containing Multiple Objects

    Directory of Open Access Journals (Sweden)

    Jamie S. North

    2017-06-01

    Full Text Available We identified the important micro-relations that are perceived when attempting to recognize patterns in stimuli consisting of multiple dynamic objects. Skilled and less-skilled participants were presented with point light display sequences representing dynamic patterns in an invasion sport and were subsequently required to make familiarity based recognition judgments in three different conditions, each of which contained only a select number of features that were present at initial viewing. No differences in recognition accuracy were observed between skilled and less-skilled participants when just objects located in the periphery were presented. Yet, when presented with the relative motions of two centrally located attacking objects only, skilled participants were significantly more accurate than less-skilled participants and their recognition accuracy improved further when a target object was included against which these relative motions could be judged. Skilled participants can perceive and recognize global patterns on the basis of centrally located relational information.

  10. The Assessment of Cognitive Emotion Regulation Strategies, Sensory Processing Sensitivity and Anxiety Sensitivity in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Esmeil Soleymani

    2016-11-01

    Full Text Available Abstract Background: The purpose of this study was to compare the cognitive emotional regulation strategies, sensory processing sensitivity and anxiety sensitivity in patients with multiple sclerosis and normal people. Materials and Methods: Statistical population of this study was all of patients with multiple sclerosis that referred to M.S association of Iran in the tehran. Sample of this study was 30 individuals of patients with multiple sclerosis selected by available sampling method and were matched with 30 individuals of normal people. Two groups completed cognitive emotion regulation, high sensory processing sensitivity and anxiety sensitivity questionnaires. Data were analyzed by one-way analysis of variance and Multivariate Analysis of Variance. Results: The results indicated that there is significant difference between two groups in view of cognitive emotion regulation strategies in which the mean of scores of patients with multiple sclerosis in maladaptive strategies of self- blame, catastrophizing and other blame were more than normal people and mean of scores of them in adaptive strategies of positive refocusing, positive reappraisal and putting into perspective were less than normal people. The results also indicated that there is a significant difference between two groups in anxiety sensitivity and sensory processing sensitivity. Conclusion: The most of emotional problems in patients with multiple sclerosis can be the result of more application of maladaptive strategies of cognitive emotion regulation, high sensory processing sensitivity and high anxiety sensitivity.

  11. Dynamics of Time Delay-Induced Multiple Synchronous Behaviors in Inhibitory Coupled Neurons

    Science.gov (United States)

    Gu, Huaguang; Zhao, Zhiguo

    2015-01-01

    The inhibitory synapse can induce synchronous behaviors different from the anti-phase synchronous behaviors, which have been reported in recent studies. In the present paper, synchronous behaviors are investigated in the motif model composed of reciprocal inhibitory coupled neurons with endogenous bursting and time delay. When coupling strength is weak, synchronous behavior appears at a single interval of time delay within a bursting period. When coupling strength is strong, multiple synchronous behaviors appear at different intervals of time delay within a bursting period. The different bursting patterns of synchronous behaviors, and time delays and coupling strengths that can induce the synchronous bursting patterns can be well interpreted by the dynamics of the endogenous bursting pattern of isolated neuron, which is acquired by the fast-slow dissection method, combined with the inhibitory coupling current. For an isolated neuron, when a negative impulsive current with suitable strength is applied at different phases of the bursting, multiple different bursting patterns can be induced. For a neuron in the motif, the inhibitory coupling current, of which the application time and strength is modulated by time delay and coupling strength, can cause single or multiple synchronous firing patterns like the negative impulsive current when time delay and coupling strength is suitable. The difference compared to the previously reported multiple synchronous behaviors that appear at time delays wider than a period of the endogenous firing is discussed. The results present novel examples of synchronous behaviors in the neuronal network with inhibitory synapses and provide a reasonable explanation. PMID:26394224

  12. Terahertz study of ultrafast carrier dynamics in InGa/GaN multiple quantum wells

    DEFF Research Database (Denmark)

    Porte, Henrik; Turchinovich, Dmitry; Cooke, David

    2009-01-01

    Ultrafast carrier dynamics in InGaN/GaN multiple quantum wells is measured by time-resolved terahertz spectroscopy. The built-in piezoelectric field is initially screened by photoexcited, polarized carriers, and is gradullay restored as the carriers recombine. We observe a nonexponential decay...... of the carrier density. Time-integrated photoluminescence spectra have shown a complete screening of the built-in piezoelectric field at high excitation fluences. We also observe that the terahertz conductivity spectra differs from simple Drude conductivity, describing the response of free carriers, and are well...

  13. Ultrafast dynamics in ZnO/ZnMgO multiple quantum wells

    International Nuclear Information System (INIS)

    Wen, X M; Davis, J A; McDonald, D; Dao, L V; Hannaford, P; Coleman, V A; Tan, H H; Jagadish, C; Koike, K; Sasa, S; Inoue, M; Yano, M

    2007-01-01

    We have investigated carrier relaxation and exciton recombination dynamics in ZnO/ZnMgO multiple quantum wells using femtosecond pump-probe techniques at room temperature. For a probe energy above the band gap, the hot carriers exhibit an effective relaxation by longitudinal optical phonon scattering with a cooling time of 700-850 fs. By detecting the emission near the band-gap, a longer decay time of a few picoseconds was observed which is attributed to acoustic phonon scattering. As the probe energy is decreased further, the decay time continues to increase due to the transitions of exciton recombination or localized carrier recombination

  14. Dynamics beetween 'old' and 'new' ethnicities and multiple identities in Sandra Cisneros' Caramelo

    Directory of Open Access Journals (Sweden)

    Branka Kalogjera

    2007-12-01

    Full Text Available The paper takes Candra Cisneros'  epic semi-biographical novel Caramelo asa literary insight into dynamics  between generations  within  a single ethnic (Chicano  community,  and compares  it against classics  of the genre in its shifting  definition  of one's  ethnic identity;  here the postmodern approach of entwining fiction and fact and awarding them equallegitimacy mirrors the possibility of embracing multiple identities, as exemplified by the novel's protagonist.

  15. Dynamical properties of the growing continuum using multiple-scale method

    Directory of Open Access Journals (Sweden)

    Hynčík L.

    2008-12-01

    Full Text Available The theory of growth and remodeling is applied to the 1D continuum. This can be mentioned e.g. as a model of the muscle fibre or piezo-electric stack. Hyperelastic material described by free energy potential suggested by Fung is used whereas the change of stiffness is taken into account. Corresponding equations define the dynamical system with two degrees of freedom. Its stability and the properties of bifurcations are studied using multiple-scale method. There are shown the conditions under which the degenerated Hopf's bifurcation is occuring.

  16. Broadband ICT policies in Southern Africa: Initiatives and dynamic spectrum regulation

    CSIR Research Space (South Africa)

    Olwal, T

    2013-05-01

    Full Text Available regulatory agencies. These ICT regulatory agencies had been established with the aim of liberalizing the telecommunications sector to ensure that governments are not the direct providers of telecom services, but the regulators [1]. Moreover, due to out... goals demand liberal and dynamic spectrum regulation policies designed at a country level and more importantly across a majority of countries in the same region. This paper highlights various initiatives aimed at formulating the all...

  17. Voltage regulator for on-board CMS ECAL powering : dynamic stability of the feedback loop

    CERN Document Server

    Wertelaers, P

    2010-01-01

    Traditionally, a capacitor is parallelled to the load of the regulator. Its main function is to steer (limit) the loop bandwidth. An ideal capacitor would provoke near-to-no dynamic stability. A typical remedy, not always elegant, is to select a device with appreciable parasitic series resistance. In this Note, and alternative method is proposed. The CMS ECAL regulator is of adjustable type, and adding a small capacitor at the divider there, brings about a "lead" type control action.

  18. Investigation of multiple visualisation techniques and dynamic queries in conjunction with direct sonification to support the browsing of audio resources

    OpenAIRE

    Brazil, Eoin

    2003-01-01

    non-peer-reviewed In this thesis, a prototype system for the browsing of audio resources was developed and an initial evaluation of this system was performed. The main contributions of this thesis are dynamic queries and multiple visualisation techniques in conjunction with direct sonification. Dynamic queries are queries that provide immediate feedback while maintaining consistency between the queries themselves and the graphical/auditory display. The multiple visualisation techniques are...

  19. Effects of Goal Relations on Self-Regulated Learning in Multiple Goal Pursuits: Performance, the Self-Regulatory Process, and Task Enjoyment

    Science.gov (United States)

    Lee, Hyunjoo

    2012-01-01

    The purpose of this study was to investigate the effects of goal relations on self-regulation in the pursuit of multiple goals, focusing on self-regulated performance, the self-regulatory process, and task enjoyment. The effect of multiple goal relations on self-regulation was explored in a set of three studies. Goal relations were divided into…

  20. Spatiotemporal regulation of ATP and Ca2+ dynamics in vertebrate rod and cone ribbon synapses.

    Science.gov (United States)

    Johnson, Jerry E; Perkins, Guy A; Giddabasappa, Anand; Chaney, Shawntay; Xiao, Weimin; White, Andrew D; Brown, Joshua M; Waggoner, Jenna; Ellisman, Mark H; Fox, Donald A

    2007-06-15

    In conventional neurons, Ca2+ enters presynaptic terminals during an action potential and its increased local concentration triggers transient exocytosis. In contrast, vertebrate photoreceptors are nonspiking neurons that maintain sustained depolarization and neurotransmitter release from ribbon synapses in darkness and produce light-dependent graded hyperpolarizing responses. Rods transmit single photon responses with high fidelity, whereas cones are less sensitive and exhibit faster response kinetics. These differences are likely due to variations in presynaptic Ca2+ dynamics. Metabolic coupling and cross-talk between mitochondria, endoplasmic reticulum (ER), plasma membrane Ca2+ ATPase (PMCA), and Na+-Ca2+ exchanger (NCX) coordinately control presynaptic ATP production and Ca2+ dynamics. The goal of our structural and functional studies was to determine the spatiotemporal regulation of ATP and Ca2+ dynamics in rod spherules and cone pedicles. Central retina tissue from C57BL/6 mice was used. Laser scanning confocal microscopy (LSCM) experiments were conducted on fixed-frozen vertical sections. Primary antibodies were selected for their tissue/cellular specificity and ability to recognize single, multiple or all splice variants of selected isoforms. Electron microscopy (EM) and 3-D electron tomography (ET) studies used our standard procedures on thin- and thick-sectioned retinas, respectively. Calibrated fluo-3-Ca2+ imaging experiments of dark- and light-adapted rod and cone terminals in retinal slices were conducted. Confocal microscopy showed that mitochondria, ER, PMCA, and NCX1 exhibited distinct retinal lamination patterns and differential distribution in photoreceptor synapses. Antibodies for three distinct mitochondrial compartments differentially labeled retinal areas with high metabolic demand: rod and cone inner segments, previously undescribed cone juxtanuclear mitochondria and the two plexiform layers. Rod spherule membranes uniformly and intensely

  1. Carbon storage regulator A contributes to the virulence of Haemophilus ducreyi in humans by multiple mechanisms.

    Science.gov (United States)

    Gangaiah, Dharanesh; Li, Wei; Fortney, Kate R; Janowicz, Diane M; Ellinger, Sheila; Zwickl, Beth; Katz, Barry P; Spinola, Stanley M

    2013-02-01

    The carbon storage regulator A (CsrA) controls a wide variety of bacterial processes, including metabolism, adherence, stress responses, and virulence. Haemophilus ducreyi, the causative agent of chancroid, harbors a homolog of csrA. Here, we generated an unmarked, in-frame deletion mutant of csrA to assess its contribution to H. ducreyi pathogenesis. In human inoculation experiments, the csrA mutant was partially attenuated for pustule formation compared to its parent. Deletion of csrA resulted in decreased adherence of H. ducreyi to human foreskin fibroblasts (HFF); Flp1 and Flp2, the determinants of H. ducreyi adherence to HFF cells, were downregulated in the csrA mutant. Compared to its parent, the csrA mutant had a significantly reduced ability to tolerate oxidative stress and heat shock. The enhanced sensitivity of the mutant to oxidative stress was more pronounced in bacteria grown to stationary phase compared to that in bacteria grown to mid-log phase. The csrA mutant also had a significant survival defect within human macrophages when the bacteria were grown to stationary phase but not to mid-log phase. Complementation in trans partially or fully restored the mutant phenotypes. These data suggest that CsrA contributes to virulence by multiple mechanisms and that these contributions may be more profound in bacterial cell populations that are not rapidly dividing in the human host.

  2. Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2018-01-01

    Full Text Available Wound healing is a complex process that involves sequential phases that overlap in time and space and affect each other dynamically at the gene and protein levels. We previously showed that insulin accelerates wound healing by stimulating faster and regenerative healing. One of the processes that insulin stimulates is an increase in monocyte/macrophage chemotaxis. In this study, we performed experiments in vivo and in vitro to elucidate the signaling transduction pathways that are involved in insulin-induced monocyte/macrophage chemotaxis. We found that insulin stimulates THP-1 cell chemotaxis in a dose-dependent and insulin receptor-dependent manner. We also show that the kinases PI3K-Akt, SPAK/JNK, and p38 MAPK are key molecules in the insulin-induced signaling pathways that lead to chemoattraction of the THP-1 cell. Furthermore, both PI3K-Akt and SPAK/JNK signaling involve Rac1 activation, an important molecule in regulating cell motility. Indeed, topical application of Rac1 inhibitor at an early stage during the healing process caused delayed and impaired healing even in the presence of insulin. These results delineate cell and molecular mechanisms involved in insulin-induced chemotaxis of monocyte/macrophage, cells that are critical for proper healing.

  3. A Comparison of Combustion Dynamics for Multiple 7-Point Lean Direct Injection Combustor Configurations

    Science.gov (United States)

    Tacina, K. M.; Hicks, Y. R.

    2017-01-01

    The combustion dynamics of multiple 7-point lean direct injection (LDI) combustor configurations are compared. LDI is a fuel-lean combustor concept for aero gas turbine engines in which multiple small fuel-air mixers replace one traditionally-sized fuel-air mixer. This 7-point LDI configuration has a circular cross section, with a center (pilot) fuel-air mixer surrounded by six outer (main) fuel-air mixers. Each fuel-air mixer consists of an axial air swirler followed by a converging-diverging venturi. A simplex fuel injector is inserted through the center of the air swirler, with the fuel injector tip located near the venturi throat. All 7 fuel-air mixers are identical except for the swirler blade angle, which varies with the configuration. Testing was done in a 5-atm flame tube with inlet air temperatures from 600 to 800 F and equivalence ratios from 0.4 to 0.7. Combustion dynamics were measured using a cooled PCB pressure transducer flush-mounted in the wall of the combustor test section.

  4. Detection of fast oscillating magnetic fields using dynamic multiple TR imaging and Fourier analysis.

    Directory of Open Access Journals (Sweden)

    Ki Hwan Kim

    Full Text Available Neuronal oscillations produce oscillating magnetic fields. There have been trials to detect neuronal oscillations using MRI, but the detectability in in vivo is still in debate. Major obstacles to detecting neuronal oscillations are (i weak amplitudes, (ii fast oscillations, which are faster than MRI temporal resolution, and (iii random frequencies and on/off intervals. In this study, we proposed a new approach for direct detection of weak and fast oscillating magnetic fields. The approach consists of (i dynamic acquisitions using multiple times to repeats (TRs and (ii an expanded frequency spectral analysis. Gradient echo echo-planar imaging was used to test the feasibility of the proposed approach with a phantom generating oscillating magnetic fields with various frequencies and amplitudes and random on/off intervals. The results showed that the proposed approach could precisely detect the weak and fast oscillating magnetic fields with random frequencies and on/off intervals. Complex and phase spectra showed reliable signals, while no meaningful signals were observed in magnitude spectra. A two-TR approach provided an absolute frequency spectrum above Nyquist sampling frequency pixel by pixel with no a priori target frequency information. The proposed dynamic multiple-TR imaging and Fourier analysis are promising for direct detection of neuronal oscillations and potentially applicable to any pulse sequences.

  5. Gaze stability, dynamic balance and participation deficits in people with multiple sclerosis at fall-risk.

    Science.gov (United States)

    Garg, Hina; Dibble, Leland E; Schubert, Michael C; Sibthorp, Jim; Foreman, K Bo; Gappmaier, Eduard

    2018-05-05

    Despite the common complaints of dizziness and demyelination of afferent or efferent pathways to and from the vestibular nuclei which may adversely affect the angular Vestibulo-Ocular Reflex (aVOR) and vestibulo-spinal function in persons with Multiple Sclerosis (PwMS), few studies have examined gaze and dynamic balance function in PwMS. 1) Determine the differences in gaze stability, dynamic balance and participation measures between PwMS and controls, 2) Examine the relationships between gaze stability, dynamic balance and participation. Nineteen ambulatory PwMS at fall-risk and 14 age-matched controls were recruited. Outcomes included (a) gaze stability [angular Vestibulo-Ocular Reflex (aVOR) gain (ratio of eye to head velocity); number of Compensatory Saccades (CS) per head rotation; CS latency; gaze position error; Coefficient of Variation (CV) of aVOR gain], (b) dynamic balance [Functional Gait Assessment, FGA; four square step test], and (c) participation [dizziness handicap inventory; activities-specific balance confidence scale]. Separate independent t-tests and Pearson's correlations were calculated. PwMS were age = 53 ± 11.7yrs and had 4.2 ± 3.3 falls/yr. PwMS demonstrated significant (pbalance and participation measures compared to controls. CV of aVOR gain and CS latency were significantly correlated with FGA. Deficits and correlations across a spectrum of disability measures highlight the relevance of gaze and dynamic balance assessment in PwMS. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  6. Combinatorial Optimization Algorithms for Dynamic Multiple Fault Diagnosis in Automotive and Aerospace Applications

    Science.gov (United States)

    Kodali, Anuradha

    In this thesis, we develop dynamic multiple fault diagnosis (DMFD) algorithms to diagnose faults that are sporadic and coupled. Firstly, we formulate a coupled factorial hidden Markov model-based (CFHMM) framework to diagnose dependent faults occurring over time (dynamic case). Here, we implement a mixed memory Markov coupling model to determine the most likely sequence of (dependent) fault states, the one that best explains the observed test outcomes over time. An iterative Gauss-Seidel coordinate ascent optimization method is proposed for solving the problem. A soft Viterbi algorithm is also implemented within the framework for decoding dependent fault states over time. We demonstrate the algorithm on simulated and real-world systems with coupled faults; the results show that this approach improves the correct isolation rate as compared to the formulation where independent fault states are assumed. Secondly, we formulate a generalization of set-covering, termed dynamic set-covering (DSC), which involves a series of coupled set-covering problems over time. The objective of the DSC problem is to infer the most probable time sequence of a parsimonious set of failure sources that explains the observed test outcomes over time. The DSC problem is NP-hard and intractable due to the fault-test dependency matrix that couples the failed tests and faults via the constraint matrix, and the temporal dependence of failure sources over time. Here, the DSC problem is motivated from the viewpoint of a dynamic multiple fault diagnosis problem, but it has wide applications in operations research, for e.g., facility location problem. Thus, we also formulated the DSC problem in the context of a dynamically evolving facility location problem. Here, a facility can be opened, closed, or can be temporarily unavailable at any time for a given requirement of demand points. These activities are associated with costs or penalties, viz., phase-in or phase-out for the opening or closing of a

  7. Connections between Future Time Perspectives and Self-Regulated Learning for Mid-Year Engineering Students: A Multiple Case Study

    Science.gov (United States)

    Chasmar, Justine

    2017-01-01

    This dissertation presents multiple studies with the purpose of understanding the connections between undergraduate engineering students' motivations, specifically students' Future Time Perspectives (FTPs) and Self-Regulated Learning (SRL). FTP refers to the views students hold about the future and how their perceptions of current tasks are…

  8. Dynamic Scaffolding of Socially Regulated Learning in a Computer-Based Learning Environment

    Science.gov (United States)

    Molenaar, Inge; Roda, Claudia; van Boxtel, Carla; Sleegers, Peter

    2012-01-01

    The aim of this study is to test the effects of dynamically scaffolding social regulation of middle school students working in a computer-based learning environment. Dyads in the scaffolding condition (N=56) are supported with computer-generated scaffolds and students in the control condition (N=54) do not receive scaffolds. The scaffolds are…

  9. Capital Regulation, Liquidity Requirements and Taxation in a Dynamic Model of Banking

    NARCIS (Netherlands)

    Di Nicolo, G.; Gamba, A.; Lucchetta, M.

    2011-01-01

    This paper formulates a dynamic model of a bank exposed to both credit and liquidity risk, which can resolve financial distress in three costly forms: fire sales, bond issuance and equity issuance. We use the model to analyze the impact of capital regulation, liquidity requirements and taxation on

  10. Dynamic Scaffolding of Socially Regulated Learning in a Computer-Based Learning Environment

    NARCIS (Netherlands)

    Molenaar, I.; Roda, Claudia; van Boxtel, Carla A.M.; Sleegers, P.J.C.

    2012-01-01

    The aim of this study is to test the effects of dynamically scaffolding social regulation of middle school students working in a computer-based learning environment. Dyads in the scaffolding condition (N = 56) are supported with computer-generated scaffolds and students in the control condition (N =

  11. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism

    DEFF Research Database (Denmark)

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill

    2015-01-01

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular...

  12. Digitalising the General Data Protection Regulation with Dynamic Condition Response Graphs

    DEFF Research Database (Denmark)

    Heuck, Emil; Hildebrandt, Thomas; Kiærulff Lerche, Rasmus

    2017-01-01

    We describe how the declarative Dynamic Condition Response (DCR) Graphs proces notation can be used to digitalise the General Data Protection Regulation (GDPR) and make a first evaluation to what extend the formalisation and associated tool for end-user modelling and simulation can be used to cla...

  13. Capital Regulation, Liquidity Requirements and Taxation in a Dynamic Model of Banking

    NARCIS (Netherlands)

    Di Nicolo, G.; Gamba, A.; Lucchetta, M.

    2011-01-01

    This paper formulates a dynamic model of a bank exposed to both credit and liquidity risk, which can resolve financial distress in three costly forms: fire sales, bond issuance ad equity issuance. We use the model to analyze the impact of capital regulation, liquidity requirements and taxation on

  14. Dynamic activity of NF-κB in multiple trauma patients and protective effects of ulinastain

    Directory of Open Access Journals (Sweden)

    LI Jun

    2012-02-01

    Full Text Available 【Abstract】Objective: To investigate the dynamic activity of NF-κB at the early stage of injury in multiple trauma patients and the protective effects of ulinastain. Methods: From January 2008 to May 2010, patients with multiple traumas admitted to our emergency department were enrolled in this study. Their age varied from 20-55 years. All enrolled patients were assigned randomly into control group (26 cases of multiple injury without ulinastain treatment, ulinastain group (25 cases of multiple injury with ulinastain treatment, and mild injury group (20 cases for basic control. The inclusion criteria for mild injury group were AIS-2005≤3, single wound, previously healthy inhospital patients without the history of surgical intervention. In addition to routine treatment, patients in ulinastain group were intravenously injected 200 000 IU of ulinastain dissolved in 100 ml of normal saline within 12 hours after injury and subsequently injected at the interval of every 8 hours for 7 days. NF-κB activity in monocytes and the level of TNF? IL-1, IL? in serum on admission (day 0, day 1, 2, 3, 4, and 7 were measured. Data were compared and analyzed between different groups. Results: NF-κB activity in monocytes and TNF? IL-1 and IL? of these patients reached peak levels at 24 hour after trauma, with gradual decrease to normal at 72 hour after trauma. NF-κB activity and levels of TNF? IL-1 and IL? were lower in ulinastain group than control one, without any significant difference between the two groups. The mean duration for systemic inflammatory response syndrome and multiple organ dysfunction syndrome was 7 d?.1 d and 10 d?.5 d in ulinastain group and control group respectively, and showed a significant difference. Conclusions: NF-κB activity in monocytes and the levels of inflammatory cytokines in multiply injured patients increased transiently at the early stage of trauma. Ulinastain may shorten the duration of systemic inflammatory

  15. Effect of fission dynamics on the spectra and multiplicities of prompt fission neutrons

    International Nuclear Information System (INIS)

    Nix, J.R.; Madland, D.G.; Sierk, A.J.

    1985-01-01

    With the goal of examining their effect on the spectra and multiplicities of the prompt neutrons emitted in fission, we discuss recent advances in a unified macroscopic-microscopic description of large-amplitude collective nuclear dynamics. The conversion of collective energy into single-particle excitation energy is calculated for a new surface-plus-window dissipation mechanism. By solving the Hamilton equations of motion for initial conditions appropriate to fission, we obtain the average fission-fragment translational kinetic energy and excitation energy. The spectra and multiplicities of the emitted neutrons, which depend critically upon the average excitation energy, are then calculated on the basis of standard nuclear evaporation theory, taking into account the average motion of the fission fragments, the distribution of fission-fragment residual nuclear temperature, the energy dependence of the cross section for the inverse process of compound-nucleus formation, and the possibility of multiple-chance fission. Some illustrative comparisons of our calculations with experimental data are shown

  16. ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics

    International Nuclear Information System (INIS)

    Fan, Zhongqi; Yu, Huimei; Cui, Ni; Kong, Xianggui; Liu, Xiaomin; Chang, Yulei; Wu, Yao; Sun, Liankun; Wang, Guangyi

    2015-01-01

    Cholangiocarcinoma responses weakly to cisplatin. Mitochondrial dynamics participate in the response to various stresses, and mainly involve mitophagy and mitochondrial fusion and fission. Bcl-2 family proteins play critical roles in orchestrating mitochondrial dynamics, and are involved in the resistance to cisplatin. Here we reported that ABT737, combined with cisplatin, can promote cholangiocarcinoma cells to undergo apoptosis. We found that the combined treatment decreased the Mcl-1 pro-survival form and increased Bak. Cells undergoing cisplatin treatment showed hyperfused mitochondria, whereas fragmentation was dominant in the mitochondria of cells exposed to the combined treatment, with higher Fis1 levels, decreased Mfn2 and OPA1 levels, increased ratio of Drp1 60 kD to 80 kD form, and more Drp1 located on mitochondria. More p62 aggregates were observed in cells with fragmented mitochondria, and they gradually translocated to mitochondria. Mitophagy was induced by the combined treatment. Knockdown p62 decreased the Drp1 ratio, increased Tom20, and increased cell viability. Our data indicated that mitochondrial dynamics play an important role in the response of cholangiocarcinoma to cisplatin. ABT737 might enhance cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics and the balance within Bcl-2 family proteins. Furthermore, p62 seems to be critical in the regulation of mitochondrial dynamics. - Highlights: • Cholangiocarcinoma may adapt to cisplatin through mitochondrial fusion. • ABT737 sensitizes cholangiocarcinoma to cisplatin by promoting fission and mitophagy. • p62 might participate in the regulation of mitochondrial fission and mitophagy

  17. A study on the multiple dynamic wavelength distribution for gigabit capable passive optical networks

    Directory of Open Access Journals (Sweden)

    Gustavo Adolfo Puerto Leguizamón

    2014-04-01

    Full Text Available This paper presents a data traffic based study aiming at evaluating the impact of dynamic wavelength allocation on a Gigabit capable Passive Optical Network (GPON. In Passive Optical Networks (PON, an Optical Line Terminal (OLT feeds different PONs in such a way that a given wavelength channel is evenly distributed between the Optical Network Units (ONU at each PON. However, PONs do not specify any kind of dynamic behavior on the way the wavelengths are allocated in the network, a completely static distribution is implemented instead. In thispaper we evaluate the network performance in terms of packet losses and throughput for a number of ONUs being out-of-profile while featuring a given percentage of traffic in excess for a fixed wavelength distribution and for multiple dynamic wavelength allocation. Results show that for a multichannel operation with four wavelengths, the network throughput increases up to a rough value of 19% while the packet losses drop from 22 % to 1.8 % as compared with a static wavelength distribution.

  18. Understanding the free energy barrier and multiple timescale dynamics of charge separation in organic photovoltaic cells.

    Science.gov (United States)

    Yan, Yaming; Song, Linze; Shi, Qiang

    2018-02-28

    By employing several lattice model systems, we investigate the free energy barrier and real-time dynamics of charge separation in organic photovoltaic (OPV) cells. It is found that the combined effects of the external electric field, entropy, and charge delocalization reduce the free energy barrier significantly. The dynamic disorder reduces charge carrier delocalization and results in the increased charge separation barrier, while the effect of static disorder is more complicated. Simulation of the real-time dynamics indicates that the free charge generation process involves multiple time scales, including an ultrafast component within hundreds of femtoseconds, an intermediate component related to the relaxation of the hot charge transfer (CT) state, and a slow component on the time scale of tens of picoseconds from the thermally equilibrated CT state. Effects of hot exciton dissociation as well as its dependence on the energy offset between the Frenkel exciton and the CT state are also analyzed. The current results indicate that only a small energy offset between the band gap and the lowest energy CT state is needed to achieve efficient free charge generation in OPV devices, which agrees with recent experimental findings.

  19. Formation Learning Control of Multiple Autonomous Underwater Vehicles With Heterogeneous Nonlinear Uncertain Dynamics.

    Science.gov (United States)

    Yuan, Chengzhi; Licht, Stephen; He, Haibo

    2017-09-26

    In this paper, a new concept of formation learning control is introduced to the field of formation control of multiple autonomous underwater vehicles (AUVs), which specifies a joint objective of distributed formation tracking control and learning/identification of nonlinear uncertain AUV dynamics. A novel two-layer distributed formation learning control scheme is proposed, which consists of an upper-layer distributed adaptive observer and a lower-layer decentralized deterministic learning controller. This new formation learning control scheme advances existing techniques in three important ways: 1) the multi-AUV system under consideration has heterogeneous nonlinear uncertain dynamics; 2) the formation learning control protocol can be designed and implemented by each local AUV agent in a fully distributed fashion without using any global information; and 3) in addition to the formation control performance, the distributed control protocol is also capable of accurately identifying the AUVs' heterogeneous nonlinear uncertain dynamics and utilizing experiences to improve formation control performance. Extensive simulations have been conducted to demonstrate the effectiveness of the proposed results.

  20. Understanding the free energy barrier and multiple timescale dynamics of charge separation in organic photovoltaic cells

    Science.gov (United States)

    Yan, Yaming; Song, Linze; Shi, Qiang

    2018-02-01

    By employing several lattice model systems, we investigate the free energy barrier and real-time dynamics of charge separation in organic photovoltaic (OPV) cells. It is found that the combined effects of the external electric field, entropy, and charge delocalization reduce the free energy barrier significantly. The dynamic disorder reduces charge carrier delocalization and results in the increased charge separation barrier, while the effect of static disorder is more complicated. Simulation of the real-time dynamics indicates that the free charge generation process involves multiple time scales, including an ultrafast component within hundreds of femtoseconds, an intermediate component related to the relaxation of the hot charge transfer (CT) state, and a slow component on the time scale of tens of picoseconds from the thermally equilibrated CT state. Effects of hot exciton dissociation as well as its dependence on the energy offset between the Frenkel exciton and the CT state are also analyzed. The current results indicate that only a small energy offset between the band gap and the lowest energy CT state is needed to achieve efficient free charge generation in OPV devices, which agrees with recent experimental findings.

  1. Nonlinear dynamic response of whole pool multiple spent fuel racks subject to three-dimensional excitations

    International Nuclear Information System (INIS)

    Zhao, Y.; Wilson, P.R.; Stevenson, J.D.

    1995-01-01

    The seismic evaluation of submerged free standing spent fuel storage racks is more complicated than most other nuclear structural systems. When subjected to three dimensional (3-D) floor seismic excitations the dynamic responses of racks in a pool are hydro dynamically coupled with each other, with the fuel assemblies water in gaps. The motion behavior of the racks is significantly different from that observed using a 3D single rack mode. Few seismic analyses using 3-D whole pool multiple rack models are available in the literature. I this paper an analysis was performed for twelve racks using potential theory for the fluid-structure interaction, and using a 3-D whole pool multi-rack finite element model developed herein. The analysis includes the potential nonlinear dynamic behavior of the impact of fuel-rack, rack-rack and rack-pool wall, the tilting or uplift and the frictional sliding of rack supports, and the impact of the rack supports to the pool floor. (author). 12 refs., 7 figs., 1 tab

  2. The Zymomonas mobilis regulator hfq contributes to tolerance against multiple lignocellulosic pretreatment inhibitors

    Directory of Open Access Journals (Sweden)

    Lu Tse-Yuan S

    2010-05-01

    mutant construction in Z. mobilis, and constructed a Gateway compatible expression plasmid for use in Z. mobilis for the first time. We have also used genetics to show Z. mobilis Hfq and S. cerevisiae Lsm proteins play important roles in resisting multiple, important industrially relevant inhibitors. The conserved nature of this global regulator offers the potential to apply insights from these fundamental studies for further industrial strain development.

  3. Intracellular Calreticulin Regulates Multiple Steps in Fibrillar Collagen Expression, Trafficking, and Processing into the Extracellular Matrix*

    OpenAIRE

    Van Duyn Graham, Lauren; Sweetwyne, Mariya T.; Pallero, Manuel A.; Murphy-Ullrich, Joanne E.

    2009-01-01

    Calreticulin (CRT), a chaperone and Ca2+ regulator, enhances wound healing, and its expression correlates with fibrosis in animal models, suggesting that CRT regulates production of the extracellular matrix. However, direct regulation of collagen matrix by CRT has not been previously demonstrated. We investigated the role of CRT in the regulation of fibrillar collagen expression, secretion, processing, and deposition in the extracellular matrix by fibroblasts. Mouse embryonic fibroblasts defi...

  4. Bayesian state space models for dynamic genetic network construction across multiple tissues.

    Science.gov (United States)

    Liang, Yulan; Kelemen, Arpad

    2016-08-01

    Construction of gene-gene interaction networks and potential pathways is a challenging and important problem in genomic research for complex diseases while estimating the dynamic changes of the temporal correlations and non-stationarity are the keys in this process. In this paper, we develop dynamic state space models with hierarchical Bayesian settings to tackle this challenge for inferring the dynamic profiles and genetic networks associated with disease treatments. We treat both the stochastic transition matrix and the observation matrix time-variant and include temporal correlation structures in the covariance matrix estimations in the multivariate Bayesian state space models. The unevenly spaced short time courses with unseen time points are treated as hidden state variables. Hierarchical Bayesian approaches with various prior and hyper-prior models with Monte Carlo Markov Chain and Gibbs sampling algorithms are used to estimate the model parameters and the hidden state variables. We apply the proposed Hierarchical Bayesian state space models to multiple tissues (liver, skeletal muscle, and kidney) Affymetrix time course data sets following corticosteroid (CS) drug administration. Both simulation and real data analysis results show that the genomic changes over time and gene-gene interaction in response to CS treatment can be well captured by the proposed models. The proposed dynamic Hierarchical Bayesian state space modeling approaches could be expanded and applied to other large scale genomic data, such as next generation sequence (NGS) combined with real time and time varying electronic health record (EHR) for more comprehensive and robust systematic and network based analysis in order to transform big biomedical data into predictions and diagnostics for precision medicine and personalized healthcare with better decision making and patient outcomes.

  5. Solving the Single-Sink, Fixed-Charge, Multiple-Choice Transportation Problem by Dynamic Programming

    DEFF Research Database (Denmark)

    Rauff Lind Christensen, Tue; Klose, Andreas; Andersen, Kim Allan

    important aspects of supplier selection, an important application of the SSFCTP, this does not reflect the real life situation. First, transportation costs faced by many companies are in fact piecewise linear. Secondly, when suppliers offer discounts, either incremental or all-unit discounts, such savings......The Single-Sink, Fixed-Charge, Multiple-Choice Transportation Problem (SSFCMCTP) is a problem with versatile applications. This problem is a generalization of the Single-Sink, Fixed-Charge Transportation Problem (SSFCTP), which has a fixed-charge, linear cost structure. However, in at least two...... are neglected in the SSFCTP. The SSFCMCTP overcome this problem by incorporating a staircase cost structure in the cost function instead of the usual one used in SSFCTP. We present a dynamic programming algorithm for the resulting problem. To enhance the performance of the generic algorithm a number...

  6. A New Chaotic System with Multiple Attractors: Dynamic Analysis, Circuit Realization and S-Box Design

    Directory of Open Access Journals (Sweden)

    Qiang Lai

    2017-12-01

    Full Text Available This paper reports about a novel three-dimensional chaotic system with three nonlinearities. The system has one stable equilibrium, two stable equilibria and one saddle node, two saddle foci and one saddle node for different parameters. One salient feature of this novel system is its multiple attractors caused by different initial values. With the change of parameters, the system experiences mono-stability, bi-stability, mono-periodicity, bi-periodicity, one strange attractor, and two coexisting strange attractors. The complex dynamic behaviors of the system are revealed by analyzing the corresponding equilibria and using the numerical simulation method. In addition, an electronic circuit is given for implementing the chaotic attractors of the system. Using the new chaotic system, an S-Box is developed for cryptographic operations. Moreover, we test the performance of this produced S-Box and compare it to the existing S-Box studies.

  7. Life cycle based dynamic assessment coupled with multiple criteria decision analysis

    DEFF Research Database (Denmark)

    Sohn, Joshua; Kalbar, Pradip; Birkved, Morten

    2017-01-01

    the service life of the building. This case study uses both the established and the coupled MCDA assessment methods to quantify and assess the balance of impacts between the production of mineral wool insulation versus the production of space heat. The use of TOPSIS method for calculating single scores......This work looks at coupling Life cycle assessment (LCA) with a dynamic inventory and multiple criteria decision analysis (MCDA) to improve the validity and reliability of single score results for complex systems. This is done using the case study of a representative Danish single family home over...... not matter which impact assessment is applied. However, for the scenarios where other impact categories vary inversely or independently from the climate change impact indicator, such as with renewable energy production, there is need for a more unconventional method, such as the TOPSIS method...

  8. Dynamic studies of multiple configurations of CERN's Antiproton Decelerator Target core under proton beam impact

    CERN Document Server

    AUTHOR|(CDS)2248381

    Antiprotons, like many other exotic particles, are produced by impacting high energy proton beams onto fixed targets. At the European Organization for Nuclear Research (CERN), this is done in the Antiproton Decelerator (AD) Facility. The engineering challenges related to the design of an optimal configuration of the AD-Target system derive from the extremely high energy depositions reached in the very thin target core as a consequence of each proton beam impact. A new target design is foreseen for operation after 2021, triggering multiple R&D activities since 2013 for this purpose. The goal of the present Master Thesis is to complement these activities with analytical and numerical calculations, delving into the phenomena associated to the dynamic response of the target core. In this context, two main studies have been carried out. First, the experimental data observed in targets subjected to low intensity proton pulses was cross-checked with analytical and computational methods for modal analysis, applie...

  9. Reconstruction of an input function from a dynamic PET water image using multiple tissue curves

    Science.gov (United States)

    Kudomi, Nobuyuki; Maeda, Yukito; Yamamoto, Yuka; Nishiyama, Yoshihiro

    2016-08-01

    Quantification of cerebral blood flow (CBF) is important for the understanding of normal and pathologic brain physiology. When CBF is assessed using PET with {{\\text{H}}2} 15O or C15O2, its calculation requires an arterial input function, which generally requires invasive arterial blood sampling. The aim of the present study was to develop a new technique to reconstruct an image derived input function (IDIF) from a dynamic {{\\text{H}}2} 15O PET image as a completely non-invasive approach. Our technique consisted of using a formula to express the input using tissue curve with rate constant parameter. For multiple tissue curves extracted from the dynamic image, the rate constants were estimated so as to minimize the sum of the differences of the reproduced inputs expressed by the extracted tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects (n  =  29) and was compared to the blood sampling method. Simulation studies were performed to examine the magnitude of potential biases in CBF and to optimize the number of multiple tissue curves used for the input reconstruction. In the PET study, the estimated IDIFs were well reproduced against the measured ones. The difference between the calculated CBF values obtained using the two methods was small as around  PET imaging. This suggests the possibility of using a completely non-invasive technique to assess CBF in patho-physiological studies.

  10. Implementation of dynamic cross-talk correction (DCTC) for MOX holdup assay measurements among multiple gloveboxes

    International Nuclear Information System (INIS)

    Nakamichi, Hideo; Nakamura, Hironobu; Mukai, Yasunobu; Kurita, Tsutomu; Beddingfield, David H.

    2012-01-01

    Plutonium holdup in gloveboxes (GBs) are measured by (passive neutron based NDA (HBAS) for the material control and accountancy (MC and A) at Plutonium Conversion Development Facility (PCDF). In the case that the GBs are installed close to one another, the cross-talk which means neutron double counting among GBs should be corrected properly. Though we used to use predetermined constants as the cross-talk correction, a new correction methodology for neutron cross-talk among the GBs with inventory changes is required for the improvement of MC and A. In order to address the issue of variable cross-talk contributions to holdup assay values, we applied a dynamic cross-talk correction (DCTC) method, based on the distributed source-term analysis approach, to obtain the actual doubles derived from the cross-talk between multiple GBs. As a result of introduction of DCTC for HBAS measurement, we could reduce source biases from the assay result by estimating the reliable doubles-counting derived from the cross-talk. Therefore, we could improve HBAS measurement uncertainty to a half of conventional system, and we are going to confirm the result. Since the DCTC methodology can be used to determine the cross-correlation among multiple inventories in small areas, it is expected that this methodology can be extended to the knowledge of safeguards by design. (author)

  11. Disordered and Multiple Destinations Path Planning Methods for Mobile Robot in Dynamic Environment

    Directory of Open Access Journals (Sweden)

    Yong-feng Dong

    2016-01-01

    Full Text Available In the smart home environment, aiming at the disordered and multiple destinations path planning, the sequencing rule is proposed to determine the order of destinations. Within each branching process, the initial feasible path set is generated according to the law of attractive destination. A sinusoidal adaptive genetic algorithm is adopted. It can calculate the crossover probability and mutation probability adaptively changing with environment at any time. According to the cultural-genetic algorithm, it introduces the concept of reducing turns by parallelogram and reducing length by triangle in the belief space, which can improve the quality of population. And the fallback strategy can help to jump out of the “U” trap effectively. The algorithm analyses the virtual collision in dynamic environment with obstacles. According to the different collision types, different strategies are executed to avoid obstacles. The experimental results show that cultural-genetic algorithm can overcome the problems of premature and convergence of original algorithm effectively. It can avoid getting into the local optimum. And it is more effective for mobile robot path planning. Even in complex environment with static and dynamic obstacles, it can avoid collision safely and plan an optimal path rapidly at the same time.

  12. An experimental investigation of a liquid cooling scheme for the low dropout voltage regulators of the multiplicity and vertex detector

    International Nuclear Information System (INIS)

    Bernardin, J.D.; Bosze, E.

    1997-10-01

    This report presents a summary of an experimental investigation of a liquid cooling system for the low dropout voltage regulators in the multiplicity and vertex detector (MVD), a device used to determine and characterize the collision location of two accelerated heavy ions. The coolant temperatures and flow rates as well as the voltage regulator operating temperatures were used to assess and optimize the performance of the proposed cooling system, identify potential assembly problems and system limitations, and provide the necessary information for designing and sizing the final MVD cooling system components. The MVD is part of the PHENIX experiment at Brookhaven RHIC

  13. [Dynamic accumulation regulation of curcumin, demethoxycurcumin and bisdemethoxyeurcumin in three strains of curcuma longae rhizome].

    Science.gov (United States)

    Li, Qing-Miao; Yang, Wen-Yu; Tang, Xue-Mei; Zhang, Mei; Zhou, Xian-Jian; Shu, Guang-Ming; Zhao, Jun-Ning; Fang, Qing-Mao

    2014-06-01

    The paper is aimed to study the dynamic accumulation regulation of curcumin (Cur), demethoxycurcumin (DMC) and bisdemethoxyeurcumin (BDMC) in three strains of Curcuma longa, and provide scientific references for formalized cultivation, timely harvesting, quality control and breeding cultivation of C. longa. The accumulation regulation of the three curcumin derivatives was basically the same in rhizome of three strains. The relative contents decreased along with plant development growing, while the accumulation per hectare increased with plant development growing. The accumulation of curcuminoids per hectare could be taken as the assessment standard for the best harvest time of C. longa. A3 was the best strain in terms of Cur and BDMC content.

  14. Behavior control in the sensorimotor loop with short-term synaptic dynamics induced by self-regulating neurons

    Directory of Open Access Journals (Sweden)

    Hazem eToutounji

    2014-05-01

    Full Text Available The behavior and skills of living systems depend on the distributed control provided by specialized and highly recurrent neural networks. Learning and memory in these systems is mediated by a set of adaptation mechanisms, known collectively as neuronal plasticity. Translating principles of recurrent neural control and plasticity to artificial agents has seen major strides, but is usually hampered by the complex interactions between the agent's body and its environment. One of the important standing issues is for the agent to support multiple stable states of behavior, so that its behavioral repertoire matches the requirements imposed by these interactions. The agent also must have the capacity to switch between these states in time scales that are comparable to those by which sensory stimulation varies. Achieving this requires a mechanism of short-term memory that allows the neurocontroller to keep track of the recent history of its input, which finds its biological counterpart in short-term synaptic plasticity. This issue is approached here by deriving synaptic dynamics in recurrent neural networks. Neurons are introduced as self-regulating units with a rich repertoire of dynamics. They exhibit homeostatic properties for certain parameter domains, which result in a set of stable states and the required short-term memory. They can also operate as oscillators, which allow them to surpass the level of activity imposed by their homeostatic operation conditions. Neural systems endowed with the derived synaptic dynamics can be utilized for the neural behavior control of autonomous mobile agents. The resulting behavior depends also on the underlying network structure, which is either engineered, or developed by evolutionary techniques. The effectiveness of these self-regulating units is demonstrated by controlling locomotion of a hexapod with eighteen degrees of freedom, and obstacle-avoidance of a wheel-driven robot.

  15. Dynamic Transcriptional Regulation of Fis in Salmonella During the Exponential Phase.

    Science.gov (United States)

    Wang, Hui; Wang, Lei; Li, Ping; Hu, Yilang; Zhang, Wei; Tang, Bo

    2015-12-01

    Fis is one of the most important global regulators and has attracted extensive research attention. Many studies have focused on comparing the Fis global regulatory networks for exploring Fis function during different growth stages, such as the exponential and stationary stages. Although the Fis protein in bacteria is mainly expressed in the exponential phase, the dynamic transcriptional regulation of Fis during the exponential phase remains poorly understood. To address this question, we used RNA-seq technology to identify the Fis-regulated genes in the S. enterica serovar Typhimurium during the early exponential phase, and qRT-PCR was performed to validate the transcriptional data. A total of 1495 Fis-regulated genes were successfully identified, including 987 Fis-repressed genes and 508 Fis-activated genes. Comparing the results of this study with those of our previous study, we found that the transcriptional regulation of Fis was diverse during the early- and mid-exponential phases. The results also showed that the strong positive regulation of Fis on Salmonella pathogenicity island genes in the mid-exponential phase transitioned into insignificant effect in the early exponential phase. To validate these results, we performed a cell infection assay and found that Δfis only exhibited a 1.49-fold decreased capacity compared with the LT2 wild-type strain, indicating a large difference from the 6.31-fold decrease observed in the mid-exponential phase. Our results provide strong evidence for a need to thoroughly understand the dynamic transcriptional regulation of Fis in Salmonella during the exponential phase.

  16. Early Prediction of Student Self-Regulation Strategies by Combining Multiple Models

    Science.gov (United States)

    Sabourin, Jennifer L.; Mott, Bradford W.; Lester, James C.

    2012-01-01

    Self-regulated learning behaviors such as goal setting and monitoring have been found to be crucial to students' success in computer-based learning environments. Consequently, understanding students' self-regulated learning behavior has been the subject of increasing interest. Unfortunately, monitoring these behaviors in real-time has proven…

  17. Comparing cluster-level dynamic treatment regimens using sequential, multiple assignment, randomized trials: Regression estimation and sample size considerations.

    Science.gov (United States)

    NeCamp, Timothy; Kilbourne, Amy; Almirall, Daniel

    2017-08-01

    Cluster-level dynamic treatment regimens can be used to guide sequential treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level dynamic treatment regimen, the treatment is potentially adapted and re-adapted over time based on changes in the cluster that could be impacted by prior intervention, including aggregate measures of the individuals or patients that compose it. Cluster-randomized sequential multiple assignment randomized trials can be used to answer multiple open questions preventing scientists from developing high-quality cluster-level dynamic treatment regimens. In a cluster-randomized sequential multiple assignment randomized trial, sequential randomizations occur at the cluster level and outcomes are observed at the individual level. This manuscript makes two contributions to the design and analysis of cluster-randomized sequential multiple assignment randomized trials. First, a weighted least squares regression approach is proposed for comparing the mean of a patient-level outcome between the cluster-level dynamic treatment regimens embedded in a sequential multiple assignment randomized trial. The regression approach facilitates the use of baseline covariates which is often critical in the analysis of cluster-level trials. Second, sample size calculators are derived for two common cluster-randomized sequential multiple assignment randomized trial designs for use when the primary aim is a between-dynamic treatment regimen comparison of the mean of a continuous patient-level outcome. The methods are motivated by the Adaptive Implementation of Effective Programs Trial which is, to our knowledge, the first-ever cluster-randomized sequential multiple assignment randomized trial in psychiatry.

  18. Circadian control of mRNA polyadenylation dynamics regulates rhythmic protein expression

    OpenAIRE

    Kojima, Shihoko; Sher-Chen, Elaine L.; Green, Carla B.

    2012-01-01

    Green and colleagues perform a global analysis of circadian-controlled poly(A) tails and identify hundreds of mRNAs that display dynamic rhythmic polyadenylation states. They identify three distinct classes of mRNAs with rhythmic poly(A) tails. Interestingly, class III mRNAs are controlled not by transcription, but by rhythmic cytoplasmic polyadenylation, and are regulated by the components of the cytoplasmic polyadenylation machinery, CPEB2 in particular, which are themselves rhythmically ex...

  19. A dynamic model for firm-response to non-credible incentive regulation regimes

    International Nuclear Information System (INIS)

    Agrell, Per J.; Grifell-Tatjé, Emili

    2016-01-01

    Economic network regulation increasingly use quantitative performance models (from econometrics and engineering) to set revenues. In theory, high-powered incentive regulation, such as revenue-caps, induces firms to cost-efficient behavior independent of underlying model. However, anecdotal evidence shows regulated firms occasionally maintaining cost-inefficiency under incentive regulation even under slumping profitability. We present a model for firm-level efficiency under a regime with a probability of failure explaining this phenomenon. The model is based on the hypothesis that the regulatory choice of method can be associated with intrinsic flaws leading to judicial repeal and replacement of it by a low-powered regime. The results show that the cost efficiency policy is proportional to the type of firm (cost of effort), value of time (discount factor) and the credibility of the method (risk of failure). A panel data set for 2000–2006 for 128 electricity distributors in Sweden is used to validate the model predictions (radical productivity slowdown, failing profitability and efficiency) at the launch and demise of a non-credible regulation method. The work highlights the fallacy of viewing incentive regulation as a method-independent instrument, a result applicable in any infrastructure regulation. - Highlights: • Incentive regulation relies on fixed revenue for operators. • In existing theory the efficiency-inducing effect is model-independent. • A dynamic game exposes the firm to a regulation that may fail. • One optimal policy is to pad cost and wait for the failure. • The Swedish DSOs show this policy 2003–2006, when the regime failed.

  20. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    Full Text Available Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected

  1. Dynamic regulation of NMDAR function in the adult brain by the stress hormone corticosterone

    Directory of Open Access Journals (Sweden)

    Yiu Chung eTse

    2012-03-01

    Full Text Available Stress and corticosteroids dynamically modulate the expression of synaptic plasticity at glutamatergic synapses in the developed brain. Together with alpha-amino-3-hydroxy-methyl-4-isoxazole propionic acid receptors (AMPAR, N-methyl-D-aspartate receptors (NMDAR are critical mediators of synaptic function and are essential for the induction of many forms of synaptic plasticity. Regulation of NMDAR function by cortisol/corticosterone (CORT may be fundamental to the effects of stress on synaptic plasticity. Recent reports of the efficacy of NMDAR antagonists in treating certain stress-associated psychopathologies further highlight the importance of understanding the regulation of NMDAR function by CORT. Knowledge of how corticosteroids regulate NMDAR function within the adult brain is relatively sparse, perhaps due to a common belief that NMDAR function is relatively stable in the adult brain. We review recent results from our laboratory and others demonstrating dynamic regulation of NMDAR function by CORT in the adult brain. In addition, we consider the issue of how differences in the early life environment may program differential sensitivity to modulation of NMDAR function by CORT and how this may influence synaptic function during stress. Findings from these studies demonstrate that NMDAR function in the adult hippocampus remains sensitive to even brief exposures to CORT and that the capacity for modulation of NMDAR may be programmed, in part, by the early life environment. Modulation of NMDAR function may contribute to dynamic regulation of synaptic plasticity and adaptation in the face of stress, however enhanced NMDAR function may be implicated in mechanisms of stress related psychopathologies including depression.

  2. The Kinesin Adaptor Calsyntenin-1 Organizes Microtubule Polarity and Regulates Dynamics during Sensory Axon Arbor Development

    Directory of Open Access Journals (Sweden)

    Mary C. Halloran

    2017-04-01

    Full Text Available Axon growth and branching, and development of neuronal polarity are critically dependent on proper organization and dynamics of the microtubule (MT cytoskeleton. MTs must organize with correct polarity for delivery of diverse cargos to appropriate subcellular locations, yet the molecular mechanisms regulating MT polarity remain poorly understood. Moreover, how an actively branching axon reorganizes MTs to direct their plus ends distally at branch points is unknown. We used high-speed, in vivo imaging of polymerizing MT plus ends to characterize MT dynamics in developing sensory axon arbors in zebrafish embryos. We find that axonal MTs are highly dynamic throughout development, and that the peripheral and central axons of sensory neurons show differences in MT behaviors. Furthermore, we show that Calsyntenin-1 (Clstn-1, a kinesin adaptor required for sensory axon branching, also regulates MT polarity in developing axon arbors. In wild type neurons the vast majority of MTs are directed in the correct plus-end-distal orientation from early stages of development. Loss of Clstn-1 causes an increase in MTs polymerizing in the retrograde direction. These misoriented MTs most often are found near growth cones and branch points, suggesting Clstn-1 is particularly important for organizing MT polarity at these locations. Together, our results suggest that Clstn-1, in addition to regulating kinesin-mediated cargo transport, also organizes the underlying MT highway during axon arbor development.

  3. Application of non-linear discretetime feedback regulators with assignable closed-loop dynamics

    Directory of Open Access Journals (Sweden)

    Dubljević Stevan

    2003-01-01

    Full Text Available In the present work the application of a new approach is demonstrated to a discrete-time state feedback regulator synthesis with feedback linearization and pole-placement for non-linear discrete-time systems. Under the simultaneous implementation of a non-linear coordinate transformation and a non-linear state feedback law computed through the solution of a system of non-linear functional equations, both the feedback linearization and pole-placement design objectives were accomplished. The non-linear state feedback regulator synthesis method was applied to a continuous stirred tank reactor (CSTR under non-isothermal operating conditions that exhibits steady-state multiplicity. The control objective was to regulate the reactor at the middle unstable steady state by manipulating the rate of input heat in the reactor. Simulation studies were performed to evaluate the performance of the proposed non-linear state feedback regulator, as it was shown a non-linear state feedback regulator clearly outperformed a standard linear one, especially in the presence of adverse disturbance under which linear regulation at the unstable steady state was not feasible.

  4. A voltage regulator system with dynamic bandwidth boosting for passive UHF RFID transponders

    International Nuclear Information System (INIS)

    Shen Jinpeng; Wang Xin'an; Liu Shan; Li Shoucheng; Ruan Zhengkun

    2013-01-01

    This paper presents a voltage regulator system for passive UHF RFID transponders, which contains a rectifier, a limiter, and a regulator. The rectifier achieves power by rectifying the incoming RF energy. Due to the huge variation of the rectified voltage, a limiter at the rectifier output is used to clamp the rectified voltage. In this paper, the design of a limiter circuit is discussed in detail, which can provide a stable limiting voltage with low sensitivity to temperature variation and process dispersion. The key aspect of the voltage regulator system is the dynamic bandwidth boosting in the regulator. By sensing the excess current that is bypassed in the limiter during periods of excess energy, the bias current as well as the bandwidth of the regulator are increased, the output supply voltage can recover quickly from line transients during the periods of no RF energy to a full blast of RF energy. This voltage regulator system is implemented in a 0.18 μm CMOS process. (semiconductor integrated circuits)

  5. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    Energy Technology Data Exchange (ETDEWEB)

    Voss, Kelsey; Amaya, Moushimi [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Mueller, Claudius [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Roberts, Brian [Leidos Health Life Sciences, 5202 Presidents Court, Suite 110, Frederick, MD (United States); Kehn-Hall, Kylene; Bailey, Charles [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Petricoin, Emanuel [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Narayanan, Aarthi, E-mail: anaraya1@gmu.edu [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States)

    2014-11-15

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells.

  6. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    International Nuclear Information System (INIS)

    Voss, Kelsey; Amaya, Moushimi; Mueller, Claudius; Roberts, Brian; Kehn-Hall, Kylene; Bailey, Charles; Petricoin, Emanuel; Narayanan, Aarthi

    2014-01-01

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells

  7. Evidence for dynamic network regulation of Drosophila photoreceptor function from mutants lacking the neurotransmitter histamine

    Directory of Open Access Journals (Sweden)

    An eDau

    2016-03-01

    Full Text Available Synaptic feedback from interneurons to photoreceptors can help to optimize visual information flow by balancing its allocation on retinal pathways under changing light conditions. But little is known about how this critical network operation is regulated dynamically. Here, we investigate this question by comparing signaling properties and performance of wild-type Drosophila R1-R6 photoreceptors to those of the hdcJK910 mutant, which lacks the neurotransmitter histamine and therefore cannot transmit information to interneurons. Recordings show that hdcJK910 photoreceptors sample similar amounts of information from naturalistic stimulation to wild-type photoreceptors, but this information is packaged in smaller responses, especially under bright illumination. Analyses reveal how these altered dynamics primarily resulted from network overload that affected hdcJK910 photoreceptors in two ways. First, the missing inhibitory histamine input to interneurons almost certainly depolarized them irrevocably, which in turn increased their excitatory feedback to hdcJK910 R1-R6s. This tonic excitation depolarized the photoreceptors to artificially high potentials, reducing their operational range. Second, rescuing histamine input to interneurons in hdcJK910 mutant also restored their normal phasic feedback modulation to R1-R6s, causing photoreceptor output to accentuate dynamic intensity differences at bright illumination, similar to the wild-type. These results provide mechanistic explanations of how synaptic feedback connections optimize information packaging in photoreceptor output and novel insight into the operation and design of dynamic network regulation of sensory neurons.

  8. Noncoding transcription by alternative rna polymerases dynamically regulates an auxin-driven chromatin loop

    KAUST Repository

    Ariel, Federico D.; Jé gu, Teddy; Latrasse, David; Romero-Barrios, Natali; Christ, Auré lie; Benhamed, Moussa; Crespi, Martí n D.

    2014-01-01

    The eukaryotic epigenome is shaped by the genome topology in three-dimensional space. Dynamic reversible variations in this epigenome structure directly influence the transcriptional responses to developmental cues. Here, we show that the Arabidopsis long intergenic noncoding RNA (lincRNA) APOLO is transcribed by RNA polymerases II and V in response to auxin, a phytohormone controlling numerous facets of plant development. This dual APOLO transcription regulates the formation of a chromatin loop encompassing the promoter of its neighboring gene PID, a key regulator of polar auxin transport. Altering APOLO expression affects chromatin loop formation, whereas RNA-dependent DNA methylation, active DNA demethylation, and Polycomb complexes control loop dynamics. This dynamic chromatin topology determines PID expression patterns. Hence, the dual transcription of a lincRNA influences local chromatin topology and directs dynamic auxin-controlled developmental outputs on neighboring genes. This mechanism likely underscores the adaptive success of plants in diverse environments and may be widespread in eukaryotes. © 2014 Elsevier Inc.

  9. Noncoding transcription by alternative rna polymerases dynamically regulates an auxin-driven chromatin loop

    KAUST Repository

    Ariel, Federico D.

    2014-08-01

    The eukaryotic epigenome is shaped by the genome topology in three-dimensional space. Dynamic reversible variations in this epigenome structure directly influence the transcriptional responses to developmental cues. Here, we show that the Arabidopsis long intergenic noncoding RNA (lincRNA) APOLO is transcribed by RNA polymerases II and V in response to auxin, a phytohormone controlling numerous facets of plant development. This dual APOLO transcription regulates the formation of a chromatin loop encompassing the promoter of its neighboring gene PID, a key regulator of polar auxin transport. Altering APOLO expression affects chromatin loop formation, whereas RNA-dependent DNA methylation, active DNA demethylation, and Polycomb complexes control loop dynamics. This dynamic chromatin topology determines PID expression patterns. Hence, the dual transcription of a lincRNA influences local chromatin topology and directs dynamic auxin-controlled developmental outputs on neighboring genes. This mechanism likely underscores the adaptive success of plants in diverse environments and may be widespread in eukaryotes. © 2014 Elsevier Inc.

  10. Polysome profiling in liver identifies dynamic regulation of endoplasmic reticulum translatome by obesity and fasting.

    Science.gov (United States)

    Fu, Suneng; Fan, Jason; Blanco, Joshua; Gimenez-Cassina, Alfredo; Danial, Nika N; Watkins, Steve M; Hotamisligil, Gökhan S

    2012-08-01

    Obesity-associated metabolic complications are generally considered to emerge from abnormalities in carbohydrate and lipid metabolism, whereas the status of protein metabolism is not well studied. Here, we performed comparative polysome and associated transcriptional profiling analyses to study the dynamics and functional implications of endoplasmic reticulum (ER)-associated protein synthesis in the mouse liver under conditions of obesity and nutrient deprivation. We discovered that ER from livers of obese mice exhibits a general reduction in protein synthesis, and comprehensive analysis of polysome-bound transcripts revealed extensive down-regulation of protein synthesis machinery, mitochondrial components, and bile acid metabolism in the obese translatome. Nutrient availability also plays an important but distinct role in remodeling the hepatic ER translatome in lean and obese mice. Fasting in obese mice partially reversed the overall translatomic differences between lean and obese nonfasted controls, whereas fasting of the lean mice mimicked many of the translatomic changes induced by the development of obesity. The strongest examples of such regulations were the reduction in Cyp7b1 and Slco1a1, molecules involved in bile acid metabolism. Exogenous expression of either gene significantly lowered plasma glucose levels, improved hepatic steatosis, but also caused cholestasis, indicating the fine balance bile acids play in regulating metabolism and health. Together, our work defines dynamic regulation of the liver translatome by obesity and nutrient availability, and it identifies a novel role for bile acid metabolism in the pathogenesis of metabolic abnormalities associated with obesity.

  11. VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle.

    Science.gov (United States)

    Cantarero, Lara; Sanz-García, Marta; Vinograd-Byk, Hadar; Renbaum, Paul; Levy-Lahad, Ephrat; Lazo, Pedro A

    2015-06-12

    Cajal bodies (CBs) are nuclear organelles associated with ribonucleoprotein functions and RNA maturation. CBs are assembled on coilin, its main scaffold protein, in a cell cycle dependent manner. The Ser-Thr VRK1 (vaccinia-related kinase 1) kinase, whose activity is also cell cycle regulated, interacts with and phosphorylates coilin regulating assembly of CBs. Coilin phosphorylation is not necessary for its interaction with VRK1, but it occurs in mitosis and regulates coilin stability. Knockdown of VRK1 or VRK1 inactivation by serum deprivation causes a loss of coilin phosphorylation in Ser184 and of CBs formation, which are rescued with an active VRK1, but not by kinase-dead VRK1. The phosphorylation of coilin in Ser184 occurs during mitosis before assembly of CBs. Loss of coilin phosphorylation results in disintegration of CBs, and of coilin degradation that is prevented by proteasome inhibitors. After depletion of VRK1, coilin is ubiquitinated in nuclei, which is partly mediated by mdm2, but its proteasomal degradation occurs in cytosol and is prevented by blocking its nuclear export. We conclude that VRK1 is a novel regulator of CBs dynamics and stability in cell cycle by protecting coilin from ubiquitination and degradation in the proteasome, and propose a model of CB dynamics.

  12. Polysome profiling in liver identifies dynamic regulation of endoplasmic reticulum translatome by obesity and fasting.

    Directory of Open Access Journals (Sweden)

    Suneng Fu

    2012-08-01

    Full Text Available Obesity-associated metabolic complications are generally considered to emerge from abnormalities in carbohydrate and lipid metabolism, whereas the status of protein metabolism is not well studied. Here, we performed comparative polysome and associated transcriptional profiling analyses to study the dynamics and functional implications of endoplasmic reticulum (ER-associated protein synthesis in the mouse liver under conditions of obesity and nutrient deprivation. We discovered that ER from livers of obese mice exhibits a general reduction in protein synthesis, and comprehensive analysis of polysome-bound transcripts revealed extensive down-regulation of protein synthesis machinery, mitochondrial components, and bile acid metabolism in the obese translatome. Nutrient availability also plays an important but distinct role in remodeling the hepatic ER translatome in lean and obese mice. Fasting in obese mice partially reversed the overall translatomic differences between lean and obese nonfasted controls, whereas fasting of the lean mice mimicked many of the translatomic changes induced by the development of obesity. The strongest examples of such regulations were the reduction in Cyp7b1 and Slco1a1, molecules involved in bile acid metabolism. Exogenous expression of either gene significantly lowered plasma glucose levels, improved hepatic steatosis, but also caused cholestasis, indicating the fine balance bile acids play in regulating metabolism and health. Together, our work defines dynamic regulation of the liver translatome by obesity and nutrient availability, and it identifies a novel role for bile acid metabolism in the pathogenesis of metabolic abnormalities associated with obesity.

  13. A dynamic-biased dual-loop-feedback CMOS LDO regulator with fast transient response

    International Nuclear Information System (INIS)

    Wang Han; Sun Maomao

    2014-01-01

    This paper presents a low-dropout regulator (LDO) for portable applications with dual-loop feedback and a dynamic bias circuit. The dual-loop feedback structure is adopted to reduce the output voltage spike and the response time of the LDO. The dynamic bias circuit enhances the slew rate at the gate of the power transistor. In addition, an adaptive miller compensation technique is employed, from which a single pole system is realized and over a 59° phase margin is achieved under the full range of the load current. The proposed LDO has been implemented in a 0.6-μm CMOS process. From the experimental results, the regulator can operate with a minimum dropout voltage of 200 mV at a maximum 300 mA load and I Q of 113 μA. The line regulation and load regulation are improved to 0.1 mV/V and 3.4 μV/mA due to the sufficient loop gain provided by the dual feedback loops. Under a full range load current step, the voltage spikes and the recovery time of the proposed LDO is reduced to 97 mV and 0.142 μs respectively. (semiconductor integrated circuits)

  14. Culture medium and growth regulators on in vitro multiplication of Psidium guajava L.

    Directory of Open Access Journals (Sweden)

    Jorge Vilchez

    2014-01-01

    Full Text Available Guava (Psidium guajava L. cultivar `Dwarf Cuban Red 18-40 EEA' has high yields. For large-scale propagation, micropropagation is a possible solution. The aim of this study was to determine the effect of two culture media, two cytokinins and an analog brasinoesteoides (DI-31 in the in vitro multiplication of this cultivar. Two culture media (MS and WPM, three concentrations of benzylaminopurine (BAP (0.5, 1.0, 1.5 mg l-1, three of kinetin (0.5, 1.0, 1.5 mg l-1 and two DI-31 (0.01 and 0.02 mg l-1 were evaluated. The variables evaluated were: number of shoots, number of leaves, shoot length and multiplication coefficient. It was found that the type of culture medium influenced the shoot multiplication of guava. The number of shoots, shoot length and multiplication coefficient were determined by the type and concentration of cytokinin added to the culture medium. With the use of WPM culture medium with 1 mg l-1 BAP It was obtained the highest values of the variables evaluated. The use of DI-31 promoted the shoot growth without affecting the multiplication coefficient. Key words: benzylaminopurine, DI-31, kinetin, guava, micropropagation, multiplication phase

  15. Stress and serial adult metamorphosis: Multiple roles for the stress axis in socially regulated sex change

    OpenAIRE

    Tessa K Solomon-Lane; Erica J Crespi; Erica J Crespi; Matthew Scott Grober; Matthew Scott Grober

    2013-01-01

    Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has ...

  16. Stress and serial adult metamorphosis: multiple roles for the stress axis in socially regulated sex change

    OpenAIRE

    Solomon-Lane, Tessa K.; Crespi, Erica J.; Grober, Matthew S.

    2013-01-01

    Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has be...

  17. Quantum critical matter. Quantum phase transitions with multiple dynamics and Weyl superconductors

    International Nuclear Information System (INIS)

    Meng, Tobias

    2012-01-01

    In this PhD thesis, the physics of quantum critical matter and exotic quantum state close to quantum phase transitions is investigated. We will focus on three different examples that highlight some of the interesting phenomena related to quantum phase transitions. Firstly, we discuss the physics of quantum phase transitions in quantum wires as a function of an external gate voltage when new subbands are activated. We find that at these transitions, strong correlations lead to the formation of an impenetrable gas of polarons, and identify criteria for possible instabilities in the spin- and charge sectors of the model. Our analysis is based on the combination of exact resummations, renormalization group techniques and Luttinger liquid approaches. Secondly, we turn to the physics of multiple divergent time scales close to a quantum critical point. Using an appropriately generalized renormalization group approach, we identify that the presence of multiple dynamics at a quantum phase transition can lead to the emergence of new critical scaling exponents and thus to the breakdown of the usual scaling schemes. We calculate the critical behavior of various thermodynamic properties and detail how unusual physics can arise. It is hoped that these results might be helpful for the interpretation of experimental scaling puzzles close to quantum critical points. Thirdly, we turn to the physics of topological transitions, and more precisely the physics of Weyl superconductors. The latter are the superconducting variant of the topologically non-trivial Weyl semimetals, and emerge at the quantum phase transition between a topological superconductor and a normal insulator upon perturbing the transition with a time reversal symmetry breaking perturbation, such as magnetism. We characterize the topological properties of Weyl superconductors and establish a topological phase diagram for a particular realization in heterostructures. We discuss the physics of vortices in Weyl

  18. Mutual Information Based Dynamic Integration of Multiple Feature Streams for Robust Real-Time LVCSR

    Science.gov (United States)

    Sato, Shoei; Kobayashi, Akio; Onoe, Kazuo; Homma, Shinichi; Imai, Toru; Takagi, Tohru; Kobayashi, Tetsunori

    We present a novel method of integrating the likelihoods of multiple feature streams, representing different acoustic aspects, for robust speech recognition. The integration algorithm dynamically calculates a frame-wise stream weight so that a higher weight is given to a stream that is robust to a variety of noisy environments or speaking styles. Such a robust stream is expected to show discriminative ability. A conventional method proposed for the recognition of spoken digits calculates the weights front the entropy of the whole set of HMM states. This paper extends the dynamic weighting to a real-time large-vocabulary continuous speech recognition (LVCSR) system. The proposed weight is calculated in real-time from mutual information between an input stream and active HMM states in a searchs pace without an additional likelihood calculation. Furthermore, the mutual information takes the width of the search space into account by calculating the marginal entropy from the number of active states. In this paper, we integrate three features that are extracted through auditory filters by taking into account the human auditory system's ability to extract amplitude and frequency modulations. Due to this, features representing energy, amplitude drift, and resonant frequency drifts, are integrated. These features are expected to provide complementary clues for speech recognition. Speech recognition experiments on field reports and spontaneous commentary from Japanese broadcast news showed that the proposed method reduced error words by 9.2% in field reports and 4.7% in spontaneous commentaries relative to the best result obtained from a single stream.

  19. Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7.

    Science.gov (United States)

    Rai, Ashutosh Kumar; Dubey, Ashutosh Prakash; Kumar, Santosh; Dutta, Debashis; Mishra, Mukti Nath; Singh, Bhupendra Narain; Tripathi, Anil Kumar

    2016-11-01

    Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In Azospirillum brasilense Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two crtE paralogs found in A. brasilense caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of crtE1 deletion was more pronounced than that of crtE2 deletion. Out of the five paralogs of rpoH in A. brasilense, overexpression of rpoH1 and rpoH2 enhanced carotenoid synthesis. Promoters of crtE2 and rpoH2 were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in Escherichia coli, we have shown that the crtE2 gene of A. brasilense Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of crtE1 was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors. Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the

  20. Dynamic analysis of piping with multiple damping mechanisms; Analisis dinamico de tuberias con multiples mecanismos de amortiguamiento

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Lopez, Pablo [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1990-12-31

    This paper describes a damping criterion that allows realizing in a more convenient form the dynamic analysis of piping and structures in general, subjected to independent stimulations, fabricated in different materials and/or damping devices. This criterion, named composed damping, is applicable to the method of modal superimposition. [Espanol] En este trabajo se describe un criterio de amortiguamiento que permite realizar en una forma mas conveniente el analisis dinamico de tuberias y estructuras en general, sujetas a excitaciones independientes, compuestas de diferentes materiales y/o mecanismos de amortiguamiento. Este criterio, denominado amortiguamiento compuesto, es aplicable en el metodo de superposicion modal.

  1. Dynamic analysis of piping with multiple damping mechanisms; Analisis dinamico de tuberias con multiples mecanismos de amortiguamiento

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Lopez, Pablo [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1989-12-31

    This paper describes a damping criterion that allows realizing in a more convenient form the dynamic analysis of piping and structures in general, subjected to independent stimulations, fabricated in different materials and/or damping devices. This criterion, named composed damping, is applicable to the method of modal superimposition. [Espanol] En este trabajo se describe un criterio de amortiguamiento que permite realizar en una forma mas conveniente el analisis dinamico de tuberias y estructuras en general, sujetas a excitaciones independientes, compuestas de diferentes materiales y/o mecanismos de amortiguamiento. Este criterio, denominado amortiguamiento compuesto, es aplicable en el metodo de superposicion modal.

  2. Regulation of Cortical Dynamic Range by Background Synaptic Noise and Feedforward Inhibition.

    Science.gov (United States)

    Khubieh, Ayah; Ratté, Stéphanie; Lankarany, Milad; Prescott, Steven A

    2016-08-01

    The cortex encodes a broad range of inputs. This breadth of operation requires sensitivity to weak inputs yet non-saturating responses to strong inputs. If individual pyramidal neurons were to have a narrow dynamic range, as previously claimed, then staggered all-or-none recruitment of those neurons would be necessary for the population to achieve a broad dynamic range. Contrary to this explanation, we show here through dynamic clamp experiments in vitro and computer simulations that pyramidal neurons have a broad dynamic range under the noisy conditions that exist in the intact brain due to background synaptic input. Feedforward inhibition capitalizes on those noise effects to control neuronal gain and thereby regulates the population dynamic range. Importantly, noise allows neurons to be recruited gradually and occludes the staggered recruitment previously attributed to heterogeneous excitation. Feedforward inhibition protects spike timing against the disruptive effects of noise, meaning noise can enable the gain control required for rate coding without compromising the precise spike timing required for temporal coding. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. ATX-2, the C. elegans Ortholog of Human Ataxin-2, Regulates Centrosome Size and Microtubule Dynamics.

    Directory of Open Access Journals (Sweden)

    Michael D Stubenvoll

    2016-09-01

    Full Text Available Centrosomes are critical sites for orchestrating microtubule dynamics, and exhibit dynamic changes in size during the cell cycle. As cells progress to mitosis, centrosomes recruit more microtubules (MT to form mitotic bipolar spindles that ensure proper chromosome segregation. We report a new role for ATX-2, a C. elegans ortholog of Human Ataxin-2, in regulating centrosome size and MT dynamics. ATX-2, an RNA-binding protein, forms a complex with SZY-20 in an RNA-independent fashion. Depleting ATX-2 results in embryonic lethality and cytokinesis failure, and restores centrosome duplication to zyg-1 mutants. In this pathway, SZY-20 promotes ATX-2 abundance, which inversely correlates with centrosome size. Centrosomes depleted of ATX-2 exhibit elevated levels of centrosome factors (ZYG-1, SPD-5, γ-Tubulin, increasing MT nucleating activity but impeding MT growth. We show that ATX-2 influences MT behavior through γ-Tubulin at the centrosome. Our data suggest that RNA-binding proteins play an active role in controlling MT dynamics and provide insight into the control of proper centrosome size and MT dynamics.

  4. Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6

    Science.gov (United States)

    Dai, Yawei; Seeger, Markus; Weng, Jingwei; Song, Song; Wang, Wenning; Tan, Yan-Wen

    2016-08-01

    Cellular informational and metabolic processes are propagated with specific membrane fusions governed by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNARE). SNARE protein Ykt6 is highly expressed in brain neurons and plays a critical role in the membrane-trafficking process. Studies suggested that Ykt6 undergoes a conformational change at the interface between its longin domain and the SNARE core. In this work, we study the conformational state distributions and dynamics of rat Ykt6 by means of single-molecule Förster Resonance Energy Transfer (smFRET) and Fluorescence Cross-Correlation Spectroscopy (FCCS). We observed that intramolecular conformational dynamics between longin domain and SNARE core occurred at the timescale ~200 μs. Furthermore, this dynamics can be regulated and even eliminated by the presence of lipid dodecylphoshpocholine (DPC). Our molecular dynamic (MD) simulations have shown that, the SNARE core exhibits a flexible structure while the longin domain retains relatively stable in apo state. Combining single molecule experiments and theoretical MD simulations, we are the first to provide a quantitative dynamics of Ykt6 and explain the functional conformational change from a qualitative point of view.

  5. Configurational and constitutional information storage: multiple dynamics in systems based on pyridyl and acyl hydrazones.

    Science.gov (United States)

    Chaur, Manuel N; Collado, Daniel; Lehn, Jean-Marie

    2011-01-03

    The C=N group of hydrazones can undergo E/Z isomerization both photochemically and thermally, allowing the generation of a closed process that can be tuned by either of these two physical stimuli. On the other hand, hydrazine-exchange reactions enable a constitutional change in a given hydrazone. The two classes of processes: 1) configurational (physically stimulated) and 2) constitutional (chemically stimulated) give access to short-term and long-term information storage, respectively. Such transformations are reported herein for two hydrazones (bis-pyridyl hydrazone and 2-pyridinecarboxaldehyde phenylhydrazone) that undergo a closed, chemically or physically driven process, and, in addition, can be locked or unlocked at will by metal-ion coordination or removal. These features also extend to acyl hydrazones derived from 2-pyridinecarboxaldehyde. Similarly to the terpydine-like hydrazones, such acyl hydrazones can undergo both constitutional and configurational changes, as well as metal-ion coordination. All these types of hydrazones represent dynamic systems capable of acting as multiple state molecular devices, in which the presence of coordination sites furthermore allows the metal ion-controlled locking and unlocking of the interconversion of the different states. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Dynamic load mitigation using dissipative elastic metamaterials with multiple Maxwell-type oscillators

    Science.gov (United States)

    Alamri, Sagr; Li, Bing; Tan, K. T.

    2018-03-01

    Dissipative elastic metamaterials have attracted increased attention in recent times. This paper presents the development of a dissipative elastic metamaterial with multiple Maxwell-type resonators for stress wave attenuation. The mechanism of the dissipation effect on the vibration characteristics is systematically investigated by mass-spring-damper models with single and dual resonators. Based on the parameter optimization, it is revealed that a broadband wave attenuation region (stopping band) can be obtained by properly utilizing interactions from resonant motions and viscoelastic effects of the Maxwell-type oscillators. The relevant numerical verifications are conducted for various cases, and excellent agreement between the numerical and theoretical frequency response functions is shown. The design of this dissipative metamaterial system is further applied for dynamic load mitigation and blast wave attenuation. Moreover, the transient response in the continuum model is designed and analyzed for more robust design. By virtue of the bandgap merging effect induced by the Maxwell-type damper, the transient blast wave can be almost completely suppressed in the low frequency range. A significantly improved performance of the proposed dissipative metamaterials for stress wave mitigation is verified in both time and frequency domains.

  7. FODA: a novel efficient multiple access protocol for highly dynamic self-organizing networks

    Science.gov (United States)

    Li, Hantao; Liu, Kai; Zhang, Jun

    2005-11-01

    Based on the concept of contention reservation for polling transmission and collision prevention strategy for collision resolution, a fair on-demand access (FODA) protocol for supporting node mobility and multihop architecture in highly dynamic self-organizing networks is proposed. In the protocol, a distributed clustering network architecture formed by self-organizing algorithm and a main idea of reserving channel resources to get polling service are adopted, so that the hidden terminal (HT) and exposed terminal (ET) problems existed in traffic transmission due to multihop architecture and wireless transmission can be eliminated completely. In addition, an improved collision prevention scheme based on binary countdown algorithm (BCA), called fair collision prevention (FCP) algorithm, is proposed to greatly eliminate unfair phenomena existed in contention access of newly active ordinary nodes and completely resolve access collisions. Finally, the performance comparison of the FODA protocol with carrier sense multiple access with collision avoidance (CSMA/CA) and polling protocols by OPNET simulation are presented. Simulation results show that the FODA protocol can overcome the disadvantages of CSMA/CA and polling protocols, and achieve higher throughput, lower average message delay and less average message dropping rate.

  8. Efficient traffic grooming with dynamic ONU grouping for multiple-OLT-based access network

    Science.gov (United States)

    Zhang, Shizong; Gu, Rentao; Ji, Yuefeng; Wang, Hongxiang

    2015-12-01

    Fast bandwidth growth urges large-scale high-density access scenarios, where the multiple Passive Optical Networking (PON) system clustered deployment can be adopted as an appropriate solution to fulfill the huge bandwidth demands, especially for a future 5G mobile network. However, the lack of interaction between different optical line terminals (OLTs) results in part of the bandwidth resources waste. To increase the bandwidth efficiency, as well as reduce bandwidth pressure at the edge of a network, we propose a centralized flexible PON architecture based on Time- and Wavelength-Division Multiplexing PON (TWDM PON). It can provide flexible affiliation for optical network units (ONUs) and different OLTs to support access network traffic localization. Specifically, a dynamic ONU grouping algorithm (DGA) is provided to obtain the minimal OLT outbound traffic. Simulation results show that DGA obtains an average 25.23% traffic gain increment under different OLT numbers within a small ONU number situation, and the traffic gain will increase dramatically with the increment of the ONU number. As the DGA can be deployed easily as an application running above the centralized control plane, the proposed architecture can be helpful to improve the network efficiency for future traffic-intensive access scenarios.

  9. Quantitative analysis of multiple biokinetic models using a dynamic water phantom: A feasibility study

    Science.gov (United States)

    Chiang, Fu-Tsai; Li, Pei-Jung; Chung, Shih-Ping; Pan, Lung-Fa; Pan, Lung-Kwang

    2016-01-01

    ABSTRACT This study analyzed multiple biokinetic models using a dynamic water phantom. The phantom was custom-made with acrylic materials to model metabolic mechanisms in the human body. It had 4 spherical chambers of different sizes, connected by 8 ditches to form a complex and adjustable water loop. One infusion and drain pole connected the chambers to an auxiliary silicon-based hose, respectively. The radio-active compound solution (TC-99m-MDP labeled) formed a sealed and static water loop inside the phantom. As clean feed water was infused to replace the original solution, the system mimicked metabolic mechanisms for data acquisition. Five cases with different water loop settings were tested and analyzed, with case settings changed by controlling valve poles located in the ditches. The phantom could also be changed from model A to model B by transferring its vertical configuration. The phantom was surveyed with a clinical gamma camera to determine the time-dependent intensity of every chamber. The recorded counts per pixel in each chamber were analyzed and normalized to compare with theoretical estimations from the MATLAB program. Every preset case was represented by uniquely defined, time-dependent, simultaneous differential equations, and a corresponding MATLAB program optimized the solutions by comparing theoretical calculations and practical measurements. A dimensionless agreement (AT) index was recommended to evaluate the comparison in each case. ATs varied from 5.6 to 48.7 over the 5 cases, indicating that this work presented an acceptable feasibility study. PMID:27286096

  10. Modern drug design: the implication of using artificial neuronal networks and multiple molecular dynamic simulations

    Science.gov (United States)

    Yakovenko, Oleksandr; Jones, Steven J. M.

    2018-01-01

    We report the implementation of molecular modeling approaches developed as a part of the 2016 Grand Challenge 2, the blinded competition of computer aided drug design technologies held by the D3R Drug Design Data Resource (https://drugdesigndata.org/). The challenge was focused on the ligands of the farnesoid X receptor (FXR), a highly flexible nuclear receptor of the cholesterol derivative chenodeoxycholic acid. FXR is considered an important therapeutic target for metabolic, inflammatory, bowel and obesity related diseases (Expert Opin Drug Metab Toxicol 4:523-532, 2015), but in the context of this competition it is also interesting due to the significant ligand-induced conformational changes displayed by the protein. To deal with these conformational changes we employed multiple simulations of molecular dynamics (MD). Our MD-based protocols were top-ranked in estimating the free energy of binding of the ligands and FXR protein. Our approach was ranked second in the prediction of the binding poses where we also combined MD with molecular docking and artificial neural networks. Our approach showed mediocre results for high-throughput scoring of interactions.

  11. The Dynamics of Multiple Pair-Wise Collisions in a Chain for Designing Optimal Shock Amplifiers

    Directory of Open Access Journals (Sweden)

    Bryan Rodgers

    2009-01-01

    Full Text Available The major focus of this work is to examine the dynamics of velocity amplification through pair-wise collisions between multiple masses in a chain, in order to develop useful machines. For instance low-cost machines based on this principle could be used for detailed, very-high acceleration shock-testing of MEMS devices. A theoretical basis for determining the number and mass of intermediate stages in such a velocity amplifier, based on simple rigid body mechanics, is proposed. The influence of mass ratios and the coefficient of restitution on the optimisation of the system is identified and investigated. In particular, two cases are examined: in the first, the velocity of the final mass in the chain (that would have the object under test mounted on it is maximised by defining the ratio of adjacent masses according to a power law relationship; in the second, the energy transfer efficiency of the system is maximised by choosing the mass ratios such that all masses except the final mass come to rest following impact. Comparisons are drawn between both cases and the results are used in proposing design guidelines for optimal shock amplifiers. It is shown that for most practical systems, a shock amplifier with mass ratios based on a power law relationship is optimal and can easily yield velocity amplifications of a factor 5–8 times. A prototype shock testing machine that was made using above principles is briefly introduced.

  12. Ultrafast conductivity dynamics in optically excited InGaN/GaN multiple quantum wells, observed by transient THz spectroscopy

    DEFF Research Database (Denmark)

    Turchinovich, Dmitry; Porte, Henrik; Cooke, David

    2010-01-01

    We investigate ultrafast carrier dynamics in photoexcited InGaN/GaN multiple quantum wells by time-resolved terahertz spectroscopy. The initially very strong built-in piezoelectric field is screened upon photoexcitation by the polarized carriers, and is gradually restored as the carriers recombine...

  13. Bayesian inference based modelling for gene transcriptional dynamics by integrating multiple source of knowledge

    Directory of Open Access Journals (Sweden)

    Wang Shu-Qiang

    2012-07-01

    Full Text Available Abstract Background A key challenge in the post genome era is to identify genome-wide transcriptional regulatory networks, which specify the interactions between transcription factors and their target genes. Numerous methods have been developed for reconstructing gene regulatory networks from expression data. However, most of them are based on coarse grained qualitative models, and cannot provide a quantitative view of regulatory systems. Results A binding affinity based regulatory model is proposed to quantify the transcriptional regulatory network. Multiple quantities, including binding affinity and the activity level of transcription factor (TF are incorporated into a general learning model. The sequence features of the promoter and the possible occupancy of nucleosomes are exploited to estimate the binding probability of regulators. Comparing with the previous models that only employ microarray data, the proposed model can bridge the gap between the relative background frequency of the observed nucleotide and the gene's transcription rate. Conclusions We testify the proposed approach on two real-world microarray datasets. Experimental results show that the proposed model can effectively identify the parameters and the activity level of TF. Moreover, the kinetic parameters introduced in the proposed model can reveal more biological sense than previous models can do.

  14. RhoGDI: multiple functions in the regulation of Rho family GTPase activities

    DEFF Research Database (Denmark)

    Dovas, Athanassios; Couchman, John R

    2005-01-01

    necessary for the correct targeting and regulation of Rho activities by conferring cues for spatial restriction, guidance and availability to effectors. These potential functions are discussed in the context of RhoGDI-associated multimolecular complexes, the newly emerged shuttling capability...... insight as to how RhoGDI exerts its effects on nucleotide binding, the membrane association-dissociation cycling of the GTPase and how these activities are controlled. Despite the initial negative roles attributed to RhoGDI, recent evidence has come to suggest that it may also act as a positive regulator...... of activities....

  15. Computational Studies of the Active and Inactive Regulatory Domains of Response Regulator PhoP Using Molecular Dynamics Simulations.

    Science.gov (United States)

    Qing, Xiao-Yu; Steenackers, Hans; Venken, Tom; De Maeyer, Marc; Voet, Arnout

    2017-11-01

    The response regulator PhoP is part of the PhoP/PhoQ two-component system, which is responsible for regulating the expression of multiple genes involved in controlling virulence, biofilm formation, and resistance to antimicrobial peptides. Therefore, modulating the transcriptional function of the PhoP protein is a promising strategy for developing new antimicrobial agents. There is evidence suggesting that phosphorylation-mediated dimerization in the regulatory domain of PhoP is essential for its transcriptional function. Disruption or stabilization of protein-protein interactions at the dimerization interface may inhibit or enhance the expression of PhoP-dependent genes. In this study, we performed molecular dynamics simulations on the active and inactive dimers and monomers of the PhoP regulatory domains, followed by pocket-detecting screenings and a quantitative hot-spot analysis in order to assess the druggability of the protein. Consistent with prior hypothesis, the calculation of the binding free energy shows that phosphorylation enhances dimerization of PhoP. Furthermore, we have identified two different putative binding sites at the dimerization active site (the α4-β5-α5 face) with energetic "hot-spot" areas, which could be used to search for modulators of protein-protein interactions. This study delivers insight into the dynamics and druggability of the dimerization interface of the PhoP regulatory domain, and may serve as a basis for the rational identification of new antimicrobial drugs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. CCR5 in Multiple Sclerosis : expression, regulation, and modulation by statins

    NARCIS (Netherlands)

    Kuipers, Hedwich Fardau

    2007-01-01

    Activation of microglia, the macrophages of the central nervous system, is a key element in multiple sclerosis (MS) lesion development and is characterized by enhanced expression of both classes of major histocompatibility complex (MHC) molecules. This enhanced expression results from increased

  17. Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions

    Science.gov (United States)

    Doyle, Andrew D.; Carvajal, Nicole; Jin, Albert; Matsumoto, Kazue; Yamada, Kenneth M.

    2015-11-01

    The physical properties of two-dimensional (2D) extracellular matrices (ECMs) modulate cell adhesion dynamics and motility, but little is known about the roles of local microenvironmental differences in three-dimensional (3D) ECMs. Here we generate 3D collagen gels of varying matrix microarchitectures to characterize their regulation of 3D adhesion dynamics and cell migration. ECMs containing bundled fibrils demonstrate enhanced local adhesion-scale stiffness and increased adhesion stability through balanced ECM/adhesion coupling, whereas highly pliable reticular matrices promote adhesion retraction. 3D adhesion dynamics are locally regulated by ECM rigidity together with integrin/ECM association and myosin II contractility. Unlike 2D migration, abrogating contractility stalls 3D migration regardless of ECM pore size. We find force is not required for clustering of activated integrins on 3D native collagen fibrils. We propose that efficient 3D migration requires local balancing of contractility with ECM stiffness to stabilize adhesions, which facilitates the detachment of activated integrins from ECM fibrils.

  18. Algorithm of dynamic regulation of a system of duct, for a high accuracy climatic system

    Science.gov (United States)

    Arbatskiy, A. A.; Afonina, G. N.; Glazov, V. S.

    2017-11-01

    Currently, major part of climatic system, are stationary in projected mode only. At the same time, many modern industrial sites, require constant or periodical changes in technological process. That is 80% of the time, the industrial site is not require ventilation system in projected mode and high precision of climatic parameters must maintain. While that not constantly is in use for climatic systems, which use in parallel for different rooms, we will be have a problem for balance of duct system. For this problem, was created the algorithm for quantity regulation, with minimal changes. Dynamic duct system: Developed of parallel control system of air balance, with high precision of climatic parameters. The Algorithm provide a permanent pressure in main duct, in different a flow of air. Therefore, the ending devises air flow have only one parameter for regulation - flaps open area. Precision of regulation increase and the climatic system provide high precision for temperature and humidity (0,5C for temperature, 5% for relative humidity). Result: The research has been made in CFD-system - PHOENICS. Results for velocity of air in duct, for pressure of air in duct for different operation mode, has been obtained. Equation for air valves positions, with different parameters for climate in room’s, has been obtained. Energy saving potential for dynamic duct system, for different types of a rooms, has been calculated.

  19. Estrogens regulate the hepatic effects of growth hormone, a hormonal interplay with multiple fates

    DEFF Research Database (Denmark)

    Fernández-Pérez, Leandro; Guerra, Borja; Díaz-Chico, Juan C

    2013-01-01

    The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk...

  20. Multiple diguanylate cyclase-coordinated regulation of pyoverdine synthesis in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Chen, Yicai; Yuan, Mingjun; Mohanty, Anee

    2015-01-01

    The nucleotide signalling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) plays an essential role in regulating microbial virulence and biofilm formation. C-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and degraded by phosphodiesterase (PDE) enzymes. One...

  1. 26 CFR 1.167(l)-3 - Multiple regulation, asset acquisitions, reorganizations, etc.

    Science.gov (United States)

    2010-04-01

    ... not using, such method of regulated accounting only with respect to property subject to the... treatment of certain property as “pre-1970 public utility property” and § 1.167(l)-1(e)(4)(ii) for...) Property not entirely subject to jurisdiction of one regulatory body—(1) In general. If a taxpayer which...

  2. Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyunjin; Ansong, Charles; McDermott, Jason E.; Gritsenko, Marina A.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.

    2011-06-28

    Background: Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results: In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions: Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.

  3. Improved Ribosome-Footprint and mRNA Measurements Provide Insights into Dynamics and Regulation of Yeast Translation

    Science.gov (United States)

    2016-02-11

    unlimited. Improved Ribosome-Footprint and mRNA Measurements Provide Insights into Dynamics and Regulation of Yeast Translation The views, opinions and...into Dynamics and Regulation of Yeast Translation Report Title Ribosome-footprint profiling provides genome-wide snapshots of translation, but...tend to slow translation. With the improved mRNA measurements, the variation attributable to translational control in exponentially growing yeast was

  4. The demography of climate-driven and density-regulated population dynamics in a perennial plant

    DEFF Research Database (Denmark)

    Dahlgren, Johan; Bengstsson, Karin; Ehrlén, Johan

    2016-01-01

    Identifying the internal and external drivers of population dynamics is a key objective in ecology, currently accentuated by the need to forecast the effects of climate change on species distributions and abundances. The interplay between environmental and density effects is one particularly...... important aspect of such forecasts. We examined the simultaneous impact of climate and intraspecific density on vital rates of the dwarf shrub Fumana procumbens over 20 yr, using generalized additive mixed models. We then analyzed effects on population dynamics using integral projection models...... to be driven solely by the environment can overestimate extinction risks if there is density dependence. We conclude that density regulation can dampen effects of climate change on Fumana population size, and discuss the need to quantify density dependence in predictions of population responses...

  5. Cognitive radio policy and regulation techno-economic studies to facilitate dynamic spectrum access

    CERN Document Server

    Holland, Oliver

    2014-01-01

    This book offers a timely reflection on how the proliferation of advanced wireless communications technologies, particularly cognitive radio (CR) can be enabled by thoroughly-considered policy and appropriate regulation. It looks at the prospects of CR from the divergent standpoints of technological development and economic market reality. The book provides a broad survey of various techno-economic and policy aspects of CR development, and provides the reader with an understanding of the complexities involved as well as a toolbox of possible solutions to enable the evolutionary leap towards successful implementation of disruptive CR technology or indeed any other novel wireless technologies. Cognitive Radio Policy and Regulation showcases the original ideas and concepts introduced into the field of CR and dynamic spectrum access policy over nearly four years of work within COST Action IC0905 TERRA, a think-tank with participants from more than 20 countries. The book’s subject matter includes: • deploymen...

  6. Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

    Science.gov (United States)

    Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

    2013-01-01

    This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

  7. Brd4 and HEXIM1: Multiple Roles in P-TEFb Regulation and Cancer

    Directory of Open Access Journals (Sweden)

    Ruichuan Chen

    2014-01-01

    Full Text Available Bromodomain-containing protein 4 (Brd4 and hexamethylene bisacetamide (HMBA inducible protein 1 (HEXIM1 are two opposing regulators of the positive transcription elongation factor b (P-TEFb, which is the master modulator of RNA polymerase II during transcriptional elongation. While Brd4 recruits P-TEFb to promoter-proximal chromatins to activate transcription, HEXIM1 sequesters P-TEFb into an inactive complex containing the 7SK small nuclear RNA. Besides regulating P-TEFb’s transcriptional activity, recent evidence demonstrates that both Brd4 and HEXIM1 also play novel roles in cell cycle progression and tumorigenesis. Here we will discuss the current knowledge on Brd4 and HEXIM1 and their implication as novel therapeutic options against cancer.

  8. Cell-cycle regulation in green algae dividing by multiple fission

    Czech Academy of Sciences Publication Activity Database

    Bišová, Kateřina; Zachleder, Vilém

    2014-01-01

    Roč. 65, č. 10 (2014), s. 2585-2602 ISSN 0022-0957 R&D Projects: GA ČR M200201205; GA MŠk LH12145 Grant - others:Centre for Algal Biotechnologies (Algatech)(CZ) CZ.1.05/2.1.00/03.0110 Institutional support: RVO:61388971 Keywords : cell cycle * regulation * growth * light Subject RIV: EE - Microbiology, Virology Impact factor: 5.526, year: 2014

  9. Engineering 1-Alkene Biosynthesis and Secretion by Dynamic Regulation in Yeast

    DEFF Research Database (Denmark)

    Zhou, Yongjin J.; Hu, Yating; Zhu, Zhiwei

    2018-01-01

    strategy to control the expression of membrane enzyme and 1-alkene production and cell growth by relieving the possible toxicity of overexpressed membrane proteins. With these efforts, the engineered yeast cell factory produced 35.3 mg/L 1-alkenes with more than 80% being secreted. This represents a 10...... product secretion. Here, we engineered the budding yeast Saccharomyces cerevisiae to produce and secrete 1-alkenes by manipulation of the fatty acid metabolism, enzyme selection, engineering the electron transfer system and expressing a transporter. Furthermore, we implemented a dynamic regulation...

  10. Pressure Regulators as Valves for Saving Compressed Air and their Influence on System Dynamics

    Directory of Open Access Journals (Sweden)

    Dvořák Lukáš

    2015-01-01

    Full Text Available Pressure regulators in the field of pneumatic mechanisms can be used as valves for saving compressed air. For example it can be used to reduce the pressure when the piston rod is retracting unloaded and thus it is possible to save some energy. However the problem is that saving valve can significantly affect the dynamics of the pneumatic system. The lower pressure in the piston rod chamber causes extension of time for retraction of the piston rod. This article compare the air consumption experimentally determined and calculated, measured curves of pressure in cylinder chambers and piston speed when saving valve is set up differently.

  11. Pressure Regulators as Valves for Saving Compressed Air and their Influence on System Dynamics

    Science.gov (United States)

    Dvořák, Lukáš; Fojtášek, Kamil

    2015-05-01

    Pressure regulators in the field of pneumatic mechanisms can be used as valves for saving compressed air. For example it can be used to reduce the pressure when the piston rod is retracting unloaded and thus it is possible to save some energy. However the problem is that saving valve can significantly affect the dynamics of the pneumatic system. The lower pressure in the piston rod chamber causes extension of time for retraction of the piston rod. This article compare the air consumption experimentally determined and calculated, measured curves of pressure in cylinder chambers and piston speed when saving valve is set up differently.

  12. MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice

    Science.gov (United States)

    Lin, Taoyan; Lin, Xia; Chen, Li; Zeng, Hui; Han, Yanjiang; Wu, Lihong; Huang, Shun; Wang, Meng; Huang, Shenhao; Xie, Raoying; Liang, Liqi; Liu, Yu; Liu, Ruiyu; Zhang, Tingting; Li, Jing; Wang, Shengchun; Sun, Penghui; Huang, Wenhua; Yao, Kaitai; Xu, Kang; Du, Tao; Xiao, Dong

    2016-01-01

    miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment. PMID:27711113

  13. Estrogens regulate the hepatic effects of Growth Hormone, a hormonal interplay with multiple fates

    Directory of Open Access Journals (Sweden)

    Leandro eFernandez-Perez

    2013-06-01

    Full Text Available The liver responds to estrogens and GH which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This cross-talk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens on GH biology can cause a dramatic impact in liver physiology during mammalian development and in adulthood. In this review, we will summarize the current status of the influence of estrogen on GH actions in liver. A better understanding of estrogen-GH interplay in liver will lead to improved therapy of children with growth disorders and of adults with GH deficiency.

  14. An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

    Science.gov (United States)

    Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

    2014-01-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

  15. An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

    Directory of Open Access Journals (Sweden)

    Cecil M Benitez

    2014-10-01

    Full Text Available The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

  16. Multiple ETS family proteins regulate PF4 gene expression by binding to the same ETS binding site.

    Directory of Open Access Journals (Sweden)

    Yoshiaki Okada

    Full Text Available In previous studies on the mechanism underlying megakaryocyte-specific gene expression, several ETS motifs were found in each megakaryocyte-specific gene promoter. Although these studies suggested that several ETS family proteins regulate megakaryocyte-specific gene expression, only a few ETS family proteins have been identified. Platelet factor 4 (PF4 is a megakaryocyte-specific gene and its promoter includes multiple ETS motifs. We had previously shown that ETS-1 binds to an ETS motif in the PF4 promoter. However, the functions of the other ETS motifs are still unclear. The goal of this study was to investigate a novel functional ETS motif in the PF4 promoter and identify proteins binding to the motif. In electrophoretic mobility shift assays and a chromatin immunoprecipitation assay, FLI-1, ELF-1, and GABP bound to the -51 ETS site. Expression of FLI-1, ELF-1, and GABP activated the PF4 promoter in HepG2 cells. Mutation of a -51 ETS site attenuated FLI-1-, ELF-1-, and GABP-mediated transactivation of the promoter. siRNA analysis demonstrated that FLI-1, ELF-1, and GABP regulate PF4 gene expression in HEL cells. Among these three proteins, only FLI-1 synergistically activated the promoter with GATA-1. In addition, only FLI-1 expression was increased during megakaryocytic differentiation. Finally, the importance of the -51 ETS site for the activation of the PF4 promoter during physiological megakaryocytic differentiation was confirmed by a novel reporter gene assay using in vitro ES cell differentiation system. Together, these data suggest that FLI-1, ELF-1, and GABP regulate PF4 gene expression through the -51 ETS site in megakaryocytes and implicate the differentiation stage-specific regulation of PF4 gene expression by multiple ETS factors.

  17. Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1.

    Science.gov (United States)

    Planche, Vincent; Koubiyr, Ismail; Romero, José E; Manjon, José V; Coupé, Pierrick; Deloire, Mathilde; Dousset, Vincent; Brochet, Bruno; Ruet, Aurélie; Tourdias, Thomas

    2018-04-01

    Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate. We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques. At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p < .01). After one year, CA4/dentate gyrus atrophy worsened (-6.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum radiatum-lacunosum-moleculare, -5.6%, p < .001 and -6.2%, p < .01, respectively). CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R 2  = 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2-lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ß = 0.87, p < .05). The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance. © 2018 Wiley Periodicals, Inc.

  18. Multiple steady states, limit cycles and chaotic attractors in evolutionary games with Logit Dynamics

    NARCIS (Netherlands)

    Hommes, C.H.; Ochea, M.I.

    2010-01-01

    This paper investigates, by means of simple, three and four strategy games, the occurrence of periodic and chaotic behaviour in a smooth version of the Best Response Dynamics, the Logit Dynamics. The main finding is that, unlike Replicator Dynamics, generic Hopf bifurcation and thus, stable limit

  19. Protein arginine methyltransferase 5 regulates multiple signaling pathways to promote lung cancer cell proliferation

    International Nuclear Information System (INIS)

    Sheng, Xiumei; Wang, Zhengxin

    2016-01-01

    Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of symmetrical dimethylation of arginine residues in proteins. WD repeat domain 77 (WDR77), also known as p44, MEP50, or WD45, forms a stoichiometric complex with PRMT5. The PRMT5/p44 complex is required for cellular proliferation of lung and prostate epithelial cells during earlier stages of development and is re-activated during prostate and lung tumorigenesis. The molecular mechanisms by which PRMT5 and p44 promote cellular proliferation are unknown. Expression of PRMT5 and p44 in lung and prostate cancer cells was silenced and their target genes were identified. The regulation of target genes was validated in various cancer cells during lung development and tumorigenesis. Altered expression of target genes was achieved by ectopic cDNA expression and shRNA-mediated silencing. PRMT5 and p44 regulate expression of a specific set of genes encoding growth and anti-growth factors, including receptor tyrosine kinases and antiproliferative proteins. Genes whose expression was suppressed by PRMT5 and p44 encoded anti-growth factors and inhibited cell growth when ectopically expressed. In contrast, genes whose expression was enhanced by PRMT5 and p44 encoded growth factors and increased cell growth when expressed. Altered expression of target genes is associated with re-activation of PRMT5 and p44 during lung tumorigenesis. Our data provide the molecular basis by which PRMT5 and p44 regulate cell growth and lay a foundation for further investigation of their role in lung tumor initiation. The online version of this article (doi:10.1186/s12885-016-2632-3) contains supplementary material, which is available to authorized users

  20. Disorders of Transcriptional Regulation: An Emerging Category of Multiple Malformation Syndromes

    Science.gov (United States)

    Izumi, Kosuke

    2016-01-01

    Some genetic disorders caused by mutations in genes encoding components of the transcriptional machinery as well as proteins involved in epigenetic modification of the genome share many overlapping features, such as facial dysmorphisms, growth problems and developmental delay/intellectual disability. As a basis for some shared phenotypic characteristics in these syndromes, a similar transcriptome disturbance, characterized by global transcriptional dysregulation, is believed to play a major role. In this review article, a general overview of gene transcription is provided, and the current knowledge of the mechanisms underlying some disorders of transcriptional regulation, such as Rubinstein- Taybi, Coffin-Siris, Cornelia de Lange, and CHOPS syndromes, are discussed. PMID:27867341

  1. Dynamic modeling and hierarchical compound control of a novel 2-DOF flexible parallel manipulator with multiple actuation modes

    Science.gov (United States)

    Liang, Dong; Song, Yimin; Sun, Tao; Jin, Xueying

    2018-03-01

    This paper addresses the problem of rigid-flexible coupling dynamic modeling and active control of a novel flexible parallel manipulator (PM) with multiple actuation modes. Firstly, based on the flexible multi-body dynamics theory, the rigid-flexible coupling dynamic model (RFDM) of system is developed by virtue of the augmented Lagrangian multipliers approach. For completeness, the mathematical models of permanent magnet synchronous motor (PMSM) and piezoelectric transducer (PZT) are further established and integrated with the RFDM of mechanical system to formulate the electromechanical coupling dynamic model (ECDM). To achieve the trajectory tracking and vibration suppression, a hierarchical compound control strategy is presented. Within this control strategy, the proportional-differential (PD) feedback controller is employed to realize the trajectory tracking of end-effector, while the strain and strain rate feedback (SSRF) controller is developed to restrain the vibration of the flexible links using PZT. Furthermore, the stability of the control algorithm is demonstrated based on the Lyapunov stability theory. Finally, two simulation case studies are performed to illustrate the effectiveness of the proposed approach. The results indicate that, under the redundant actuation mode, the hierarchical compound control strategy can guarantee the flexible PM achieves singularity-free motion and vibration attenuation within task workspace simultaneously. The systematic methodology proposed in this study can be conveniently extended for the dynamic modeling and efficient controller design of other flexible PMs, especially the emerging ones with multiple actuation modes.

  2. Multiple Signaling Pathways Coordinately Regulate Forgetting of Olfactory Adaptation through Control of Sensory Responses in Caenorhabditis elegans.

    Science.gov (United States)

    Kitazono, Tomohiro; Hara-Kuge, Sayuri; Matsuda, Osamu; Inoue, Akitoshi; Fujiwara, Manabi; Ishihara, Takeshi

    2017-10-18

    invertebrates. We found that in Caenorhabditis elegans hermaphrodite, the noncell autonomous regulations of forgetting of olfactory adaptation is regulated by three conserved proteins: a membrane protein, MACO-1; a receptor tyrosine kinase, SCD-2: and its ligand, HEN-1. MACO-1 and SCD-2/HEN-1, working in coordination, accelerate forgetting by controlling sensory responses in parallel. Furthermore, temporal regulation of neuronal activity is important for proper forgetting. We suggest that multiple pathways may coordinately and temporally regulate forgetting through control of sensory responses. This study should lead to a better understanding of forgetting in higher organisms. Copyright © 2017 the authors 0270-6474/17/3710240-12$15.00/0.

  3. Multiple ketolases involved in light regulation of canthaxanthin biosynthesis in Nostoc punctiforme PCC 73102.

    Science.gov (United States)

    Schöpf, Lotte; Mautz, Jürgen; Sandmann, Gerhard

    2013-05-01

    In the genome of Nostoc punctiforme PCC 73102, three functional β-carotene ketolase genes exist, one of the crtO and two of the crtW type. They were all expressed and their corresponding enzymes were functional inserting 4-keto groups into β-carotene as shown by functional pathway complementation in Escherichia coli. They all synthesized canthaxanthin but with different efficiencies. Canthaxanthin is the photoprotective carotenoid of N. punctiforme PCC 73102. Under high-light stress, its synthesis was enhanced. This was caused by up-regulation of the transcripts of two genes in combination. The first crtB-encoding phytoene synthase is the gate way enzyme of carotenogenesis resulting in an increased inflow into the pathway. The second was the ketolase gene crtW148 which in high light takes over β-carotene conversion into canthaxanthin from the other ketolases. The other ketolases were down-regulated under high-light conditions. CrtW148 was also exclusively responsible for the last step in 4-keto-myxoxanthophyll synthesis.

  4. Environmental emergency response plans (EERPs): A single plan approach to satisfy multiple regulations

    International Nuclear Information System (INIS)

    Muzyka, L.

    1995-01-01

    Conrail is a freight railroad operating in twelve northeast and midwestern states transporting goods and materials over 11,700 miles of railroad. To repair, maintain, rebuild, and manufacture locomotives and rail cars, and to maintain the track, right of way, bridges, tunnels and other structures, Conrail uses petroleum products, solvents and cleaners. These products are stored in hundreds of storage tanks in and around the yards and right of way. To power the trains, locomotives are fueled with diesel fuel. With large volumes of fuel, lubricants, solvents and cleaners, safe and efficient handling of petroleum and chemicals is crucial to avoid negative impacts on the environment. Conrail recently revisited the issue of environmental emergency response planning. In an attempt to assure full compliance with a myriad of federal, state, and local regulation, a ''single plan approach'' was chosen. Single plans for each facility, coined EERPs, were decided on after careful review of the regulations, and evaluation of the company's operational and organizational needs

  5. Dynamic hubs show competitive and static hubs non-competitive regulation of their interaction partners.

    Directory of Open Access Journals (Sweden)

    Apurv Goel

    Full Text Available Date hub proteins have 1 or 2 interaction interfaces but many interaction partners. This raises the question of whether all partner proteins compete for the interaction interface of the hub or if the cell carefully regulates aspects of this process? Here, we have used real-time rendering of protein interaction networks to analyse the interactions of all the 1 or 2 interface hubs of Saccharomyces cerevisiae during the cell cycle. By integrating previously determined structural and gene expression data, and visually hiding the nodes (proteins and their edges (interactions during their troughs of expression, we predict when interactions of hubs and their partners are likely to exist. This revealed that 20 out of all 36 one- or two- interface hubs in the yeast interactome fell within two main groups. The first was dynamic hubs with static partners, which can be considered as 'competitive hubs'. Their interaction partners will compete for the interaction interface of the hub and the success of any interaction will be dictated by the kinetics of interaction (abundance and affinity and subcellular localisation. The second was static hubs with dynamic partners, which we term 'non-competitive hubs'. Regulatory mechanisms are finely tuned to lessen the presence and/or effects of competition between the interaction partners of the hub. It is possible that these regulatory processes may also be used by the cell for the regulation of other, non-cell cycle processes.

  6. Caudal regulates the spatiotemporal dynamics of pair-rule waves in Tribolium.

    Directory of Open Access Journals (Sweden)

    Ezzat El-Sherif

    2014-10-01

    Full Text Available In the short-germ beetle Tribolium castaneum, waves of pair-rule gene expression propagate from the posterior end of the embryo towards the anterior and eventually freeze into stable stripes, partitioning the anterior-posterior axis into segments. Similar waves in vertebrates are assumed to arise due to the modulation of a molecular clock by a posterior-to-anterior frequency gradient. However, neither a molecular candidate nor a functional role has been identified to date for such a frequency gradient, either in vertebrates or elsewhere. Here we provide evidence that the posterior gradient of Tc-caudal expression regulates the oscillation frequency of pair-rule gene expression in Tribolium. We show this by analyzing the spatiotemporal dynamics of Tc-even-skipped expression in strong and mild knockdown of Tc-caudal, and by correlating the extension, level and slope of the Tc-caudal expression gradient to the spatiotemporal dynamics of Tc-even-skipped expression in wild type as well as in different RNAi knockdowns of Tc-caudal regulators. Further, we show that besides its absolute importance for stripe generation in the static phase of the Tribolium blastoderm, a frequency gradient might serve as a buffer against noise during axis elongation phase in Tribolium as well as vertebrates. Our results highlight the role of frequency gradients in pattern formation.

  7. ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation

    Directory of Open Access Journals (Sweden)

    Timothy J. Mead

    2018-04-01

    Full Text Available Summary: Focal adhesions anchor cells to extracellular matrix (ECM and direct assembly of a pre-stressed actin cytoskeleton. They act as a cellular sensor and regulator, linking ECM to the nucleus. Here, we identify proteolytic turnover of the anti-adhesive proteoglycan versican as a requirement for maintenance of smooth muscle cell (SMC focal adhesions. Using conditional deletion in mice, we show that ADAMTS9, a secreted metalloprotease, is required for myometrial activation during late gestation and for parturition. Through knockdown of ADAMTS9 in uterine SMC, and manipulation of pericellular versican via knockdown or proteolysis, we demonstrate that regulated pericellular matrix dynamics is essential for focal adhesion maintenance. By influencing focal adhesion formation, pericellular versican acts upstream of cytoskeletal assembly and SMC differentiation. Thus, pericellular versican proteolysis by ADAMTS9 balances pro- and anti-adhesive forces to maintain an SMC phenotype, providing a concrete example of the dynamic reciprocity of cells and their ECM. : Mead et al. identify a proteolytic mechanism that actively maintains a pericellular microenvironment conducive to uterine smooth muscle activation prior to parturition. They show that pericellular matrix proteolysis by the secreted metalloprotease ADAMTS9 is crucial for maintenance of focal adhesions in uterine smooth muscle cells, and its absence impairs parturition. Keywords: metalloprotease, extracellular matrix, smooth muscle, proteoglycan, myometrium, parturition, uterus, focal adhesion, proteolysis, interference reflection microscopy

  8. Cellular volume regulation and substrate stiffness modulate the detachment dynamics of adherent cells

    Science.gov (United States)

    Yang, Yuehua; Jiang, Hongyuan

    2018-03-01

    Quantitative characterizations of cell detachment are vital for understanding the fundamental mechanisms of cell adhesion. Experiments have found that cell detachment shows strong rate dependence, which is mostly attributed to the binding-unbinding kinetics of receptor-ligand bond. However, our recent study showed that the cellular volume regulation can significantly regulate the dynamics of adherent cell and cell detachment. How this cellular volume regulation contributes to the rate dependence of cell detachment remains elusive. Here, we systematically study the role of cellular volume regulation in the rate dependence of cell detachment by investigating the cell detachments of nonspecific adhesion and specific adhesion. We find that the cellular volume regulation and the bond kinetics dominate the rate dependence of cell detachment at different time scales. We further test the validity of the traditional Johnson-Kendall-Roberts (JKR) contact model and the detachment model developed by Wyart and Gennes et al (W-G model). When the cell volume is changeable, the JKR model is not appropriate for both the detachments of convex cells and concave cells. The W-G model is valid for the detachment of convex cells but is no longer applicable for the detachment of concave cells. Finally, we show that the rupture force of adherent cells is also highly sensitive to substrate stiffness, since an increase in substrate stiffness will lead to more associated bonds. These findings can provide insight into the critical role of cell volume in cell detachment and might have profound implications for other adhesion-related physiological processes.

  9. A Hox Gene, Antennapedia, Regulates Expression of Multiple Major Silk Protein Genes in the Silkworm Bombyx mori.

    Science.gov (United States)

    Tsubota, Takuya; Tomita, Shuichiro; Uchino, Keiro; Kimoto, Mai; Takiya, Shigeharu; Kajiwara, Hideyuki; Yamazaki, Toshimasa; Sezutsu, Hideki

    2016-03-25

    Hoxgenes play a pivotal role in the determination of anteroposterior axis specificity during bilaterian animal development. They do so by acting as a master control and regulating the expression of genes important for development. Recently, however, we showed that Hoxgenes can also function in terminally differentiated tissue of the lepidopteranBombyx mori In this species,Antennapedia(Antp) regulates expression of sericin-1, a major silk protein gene, in the silk gland. Here, we investigated whether Antpcan regulate expression of multiple genes in this tissue. By means of proteomic, RT-PCR, and in situ hybridization analyses, we demonstrate that misexpression of Antpin the posterior silk gland induced ectopic expression of major silk protein genes such assericin-3,fhxh4, and fhxh5 These genes are normally expressed specifically in the middle silk gland as is Antp Therefore, the evidence strongly suggests that Antpactivates these silk protein genes in the middle silk gland. The putativesericin-1 activator complex (middle silk gland-intermolt-specific complex) can bind to the upstream regions of these genes, suggesting that Antpdirectly activates their expression. We also found that the pattern of gene expression was well conserved between B. moriand the wild species Bombyx mandarina, indicating that the gene regulation mechanism identified here is an evolutionarily conserved mechanism and not an artifact of the domestication of B. mori We suggest that Hoxgenes have a role as a master control in terminally differentiated tissues, possibly acting as a primary regulator for a range of physiological processes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Spatial heterogeneity regulates plant-pollinator networks across multiple landscape scales.

    Directory of Open Access Journals (Sweden)

    Eduardo Freitas Moreira

    Full Text Available Mutualistic plant-pollinator interactions play a key role in biodiversity conservation and ecosystem functioning. In a community, the combination of these interactions can generate emergent properties, e.g., robustness and resilience to disturbances such as fluctuations in populations and extinctions. Given that these systems are hierarchical and complex, environmental changes must have multiple levels of influence. In addition, changes in habitat quality and in the landscape structure are important threats to plants, pollinators and their interactions. However, despite the importance of these phenomena for the understanding of biological systems, as well as for conservation and management strategies, few studies have empirically evaluated these effects at the network level. Therefore, the objective of this study was to investigate the influence of local conditions and landscape structure at multiple scales on the characteristics of plant-pollinator networks. This study was conducted in agri-natural lands in Chapada Diamantina, Bahia, Brazil. Pollinators were collected in 27 sampling units distributed orthogonally along a gradient of proportion of agriculture and landscape diversity. The Akaike information criterion was used to select models that best fit the metrics for network characteristics, comparing four hypotheses represented by a set of a priori candidate models with specific combinations of the proportion of agriculture, the average shape of the landscape elements, the diversity of the landscape and the structure of local vegetation. The results indicate that a reduction of habitat quality and landscape heterogeneity can cause species loss and decrease of networks nestedness. These structural changes can reduce robustness and resilience of plant-pollinator networks what compromises the reproductive success of plants, the maintenance of biodiversity and the pollination service stability. We also discuss the possible explanations for

  11. Spatial heterogeneity regulates plant-pollinator networks across multiple landscape scales.

    Science.gov (United States)

    Moreira, Eduardo Freitas; Boscolo, Danilo; Viana, Blandina Felipe

    2015-01-01

    Mutualistic plant-pollinator interactions play a key role in biodiversity conservation and ecosystem functioning. In a community, the combination of these interactions can generate emergent properties, e.g., robustness and resilience to disturbances such as fluctuations in populations and extinctions. Given that these systems are hierarchical and complex, environmental changes must have multiple levels of influence. In addition, changes in habitat quality and in the landscape structure are important threats to plants, pollinators and their interactions. However, despite the importance of these phenomena for the understanding of biological systems, as well as for conservation and management strategies, few studies have empirically evaluated these effects at the network level. Therefore, the objective of this study was to investigate the influence of local conditions and landscape structure at multiple scales on the characteristics of plant-pollinator networks. This study was conducted in agri-natural lands in Chapada Diamantina, Bahia, Brazil. Pollinators were collected in 27 sampling units distributed orthogonally along a gradient of proportion of agriculture and landscape diversity. The Akaike information criterion was used to select models that best fit the metrics for network characteristics, comparing four hypotheses represented by a set of a priori candidate models with specific combinations of the proportion of agriculture, the average shape of the landscape elements, the diversity of the landscape and the structure of local vegetation. The results indicate that a reduction of habitat quality and landscape heterogeneity can cause species loss and decrease of networks nestedness. These structural changes can reduce robustness and resilience of plant-pollinator networks what compromises the reproductive success of plants, the maintenance of biodiversity and the pollination service stability. We also discuss the possible explanations for these relationships and

  12. Dynamical and technological consequences of multiple isolas of steady states in a catalytic fluidised-bed reactor

    Directory of Open Access Journals (Sweden)

    Bizon Katarzyna

    2017-09-01

    Full Text Available Steady-state characteristics of a catalytic fluidised bed reactor and its dynamical consequences are analyzed. The occurrence of an untypical steady-state structure manifesting in a form of multiple isolas is described. A two-phase bubbling bed model is used for a quantitative description of the bed of catalyst. The influence of heat exchange intensity and a fluidisation ratio onto the generation of isolated solution branches is presented for two kinetic schemes. Dynamical consequences of the coexistence of such untypical branches of steady states are presented. The impact of linear growth of the fluidisation ratio and step change of the cooling medium temperature onto the desired product yield is analyzed. The results presented in this study confirm that the identification of a region of the occurrence of multiple isolas is important due to their strong impact both on the process start-up and its control.

  13. Multiple Object Permanence Tracking: Maintenance, Retrieval and Transformation of Dynamic Object Representations

    OpenAIRE

    Saiki, Jun

    2008-01-01

    Multiple object permanence tracking (MOPT) task revealed that our ability of maintaining and transforming multiple representations of complex feature-bound objects is limited to handle only 1-2 objects. Often reported capacity of 3-5 objects likely reflects memory for partial representations of objects and simple cases such as just color and their locations. Also, performance in multiple object tracking (MOT) task is likely mediated by spatiotemporal indices, not by feature-bound object repre...

  14. [HSP90 Inhibitor 17-AAG Inhibits Multiple Myeloma Cell Proliferation by Down-regulating Wnt/β-Catenin Signaling Pathway].

    Science.gov (United States)

    Chen, Kan-Kan; He, Zheng-Mei; Ding, Bang-He; Chen, Yue; Zhang, Li-Juan; Yu, Liang; Gao, Jian

    2016-02-01

    To investigate the inhibitory effect of HSP90 inhibitory 17-AAG on proliferation of multiple myeloma cells and its main mechanism. The multiple myeloma cells U266 were treated with 17-AAG of different concentrations (200, 400, 600 and 800 nmol/L) for 24, 48, and 72 hours respectively, then the proliferation rate, expression levels of β-catenin and C-MYC protein, as well as cell cycle of U266 cells were treated with 17-AAG and were detected by MTT method, Western blot and flow cytometry, respectively. The 17-AAG showed inhibitory effect on the proliferation of U266 cells in dose- and time-depetent manners (r = -0.518, P AAG displayed no inhibitory effect on proliferation of U266 cells (P > 0.05). The result of culturing U266 cells for 72 hours by 17-AAG of different concentrations showed that the more high of 17-AAG concentration, the more low level of β-catenin and C-MYC proteins (P AAG concentration, the more high of cell ratio in G1 phase (P AAG, the more long time of culture, the more high of cell ratio in G1 phase (P AAG can inhibit the proliferation of multiple myeloma cells, the down-regulation of Wnt/β-catenin signaling pathway and inhibition of HSP90 expression may be the main mechnisms of 17-AAG effect.

  15. The multiple functions of the endocannabinoid system: a focus on the regulation of food intake

    Directory of Open Access Journals (Sweden)

    Tibiriça Eduardo

    2010-01-01

    Full Text Available Abstract Background Cannabis sativa (also known as marijuana has been cultivated by man for more than 5,000 years. However, there was a rise in its use in the 20th century for recreational, religious or spiritual, and medicinal purposes. The main psychoactive constituent of cannabis, whose structure was identified in the 1960's, is Δ9-tetrahydrocannabinol. On the other hand, the discovery of cannabinoid receptors and their endogenous agonists took place only very recently. In fact, the first cannabinoid receptor (CB1 was cloned in 1990, followed 3 years later by the characterization of a second cannabinoid receptor (CB2. Since the 19th century, the use of cannabis has been reported to stimulate appetite and increase the consumption of sweet and tasty food, sometimes resulting in significant weight gain. The recent description of the endocannabinoid system, not only in the central nervous system but also in peripheral tissues, points to its involvement in the regulation of appetite, food intake and energy metabolism. Consequently, the pharmacological modulation of the over-activity of this system could be useful in the treatment of the metabolic syndrome. Conclusions The endocannabinoid system has important physiological functions not only in the central nervous system but also in peripheral tissues. The activation of central CB1 receptors, particularly in hypothalamic nuclei and in the limbic system, is involved in the regulation of feeding behavior, and especially in the control of the intake of palatable food. In the periphery, cannabinoid receptors are present in adipocytes, skeletal muscle, gastrointestinal tract and liver, modulating energy metabolism.

  16. Nucleophosmin/B23 regulates ubiquitin dynamics in nucleoli by recruiting deubiquitylating enzyme USP36.

    Science.gov (United States)

    Endo, Akinori; Kitamura, Naomi; Komada, Masayuki

    2009-10-09

    The nucleolus is a subnuclear compartment with multiple cellular functions, including ribosome biogenesis. USP36 is a deubiquitylating enzyme that localizes to nucleoli and plays an essential role in regulating the structure and function of the organelle. However, how the localization of USP36 is regulated remains unknown. Here, we identified a short stretch of basic amino acids (RGKEKKIKKFKREKRR) that resides in the C-terminal region of USP36 and serves as a nucleolar localization signal for the protein. We found that this motif interacts with a central acidic region of nucleophosmin/B23, a major nucleolar protein involved in various nucleolar functions. Knockdown of nucleophosmin/B23 resulted in a significant reduction in the amount of USP36 in nucleoli, without affecting the cellular USP36 level. This was associated with elevated ubiquitylation levels of fibrillarin, a USP36 substrate protein in nucleoli. We conclude that nucleophosmin/B23 recruits USP36 to nucleoli, thereby serving as a platform for the regulation of nucleolar protein functions through ubiquitylation/deubiquitylation.

  17. The Effects of Multiple-Joint Isokinetic Resistance Training on Maximal Isokinetic and Dynamic Muscle Strength and Local Muscular Endurance.

    Science.gov (United States)

    Ratamess, Nicholas A; Beller, Noah A; Gonzalez, Adam M; Spatz, Gregory E; Hoffman, Jay R; Ross, Ryan E; Faigenbaum, Avery D; Kang, Jie

    2016-03-01

    The transfer of training effects of multiple-joint isokinetic resistance training to dynamic exercise performance remain poorly understood. Thus, the purpose of the present study was to investigate the magnitude of isokinetic and dynamic one repetition-maximum (1RM) strength and local muscular endurance increases after 6 weeks of multiple-joint isokinetic resistance training. Seventeen women were randomly assigned to either an isokinetic resistance training group (IRT) or a non-exercising control group (CTL). The IRT group underwent 6 weeks of training (2 days per week) consisting of 5 sets of 6-10 repetitions at 75-85% of subjects' peak strength for the isokinetic chest press and seated row exercises at an average linear velocity of 0.15 m s(-1) [3-sec concentric (CON) and 3-sec eccentric (ECC) phases]. Peak CON and ECC force during the chest press and row, 1RM bench press and bent-over row, and maximum number of modified push-ups were assessed pre and post training. A 2 x 2 analysis of variance with repeated measures and Tukey's post hoc tests were used for data analysis. The results showed that 1RM bench press (from 38.6 ± 6.7 to 43.0 ± 5.9 kg), 1RM bent-over row (from 40.4 ± 7.7 to 45.5 ± 7.5 kg), and the maximal number of modified push-ups (from 39.5 ± 13.6 to 55.3 ± 13.1 repetitions) increased significantly only in the IRT group. Peak isokinetic CON and ECC force in the chest press and row significantly increased in the IRT group. No differences were shown in the CTL group for any measure. These data indicate 6 weeks of multiple-joint isokinetic resistance training increases dynamic muscle strength and local muscular endurance performance in addition to specific isokinetic strength gains in women. Key pointsMultiple-joint isokinetic resistance training increases dynamic maximal muscular strength, local muscular endurance, and maximal isokinetic strength in women.Multiple-joint isokinetic resistance training increased 1RM strength in the bench press (by

  18. The Effects of Multiple-Joint Isokinetic Resistance Training on Maximal Isokinetic and Dynamic Muscle Strength and Local Muscular Endurance

    Science.gov (United States)

    Ratamess, Nicholas A.; Beller, Noah A.; Gonzalez, Adam M.; Spatz, Gregory E.; Hoffman, Jay R.; Ross, Ryan E.; Faigenbaum, Avery D.; Kang, Jie

    2016-01-01

    The transfer of training effects of multiple-joint isokinetic resistance training to dynamic exercise performance remain poorly understood. Thus, the purpose of the present study was to investigate the magnitude of isokinetic and dynamic one repetition-maximum (1RM) strength and local muscular endurance increases after 6 weeks of multiple-joint isokinetic resistance training. Seventeen women were randomly assigned to either an isokinetic resistance training group (IRT) or a non-exercising control group (CTL). The IRT group underwent 6 weeks of training (2 days per week) consisting of 5 sets of 6-10 repetitions at 75-85% of subjects’ peak strength for the isokinetic chest press and seated row exercises at an average linear velocity of 0.15 m s-1 [3-sec concentric (CON) and 3-sec eccentric (ECC) phases]. Peak CON and ECC force during the chest press and row, 1RM bench press and bent-over row, and maximum number of modified push-ups were assessed pre and post training. A 2 x 2 analysis of variance with repeated measures and Tukey’s post hoc tests were used for data analysis. The results showed that 1RM bench press (from 38.6 ± 6.7 to 43.0 ± 5.9 kg), 1RM bent-over row (from 40.4 ± 7.7 to 45.5 ± 7.5 kg), and the maximal number of modified push-ups (from 39.5 ± 13.6 to 55.3 ± 13.1 repetitions) increased significantly only in the IRT group. Peak isokinetic CON and ECC force in the chest press and row significantly increased in the IRT group. No differences were shown in the CTL group for any measure. These data indicate 6 weeks of multiple-joint isokinetic resistance training increases dynamic muscle strength and local muscular endurance performance in addition to specific isokinetic strength gains in women. Key points Multiple-joint isokinetic resistance training increases dynamic maximal muscular strength, local muscular endurance, and maximal isokinetic strength in women. Multiple-joint isokinetic resistance training increased 1RM strength in the bench press

  19. Multiple scattering of MeV ions: Comparison between the analytical theory and Monte-Carlo and molecular dynamics simulations

    International Nuclear Information System (INIS)

    Mayer, M.; Arstila, K.; Nordlund, K.; Edelmann, E.; Keinonen, J.

    2006-01-01

    Angular and energy distributions due to multiple small angle scattering were calculated with different models, namely from the analytical Szilagyi theory, the Monte-Carlo code MCERD in binary collision approximation and the molecular dynamics code MDRANGE, for 2 MeV 4 He in Au at backscattering geometry and for 20 MeV 127 I recoil analysis of carbon. The widths and detailed shapes of the distributions are compared, and reasons for deviations between the different models are discussed

  20. Regulation of an Autoimmune Model for Multiple Sclerosis in Th2-Biased GATA3 Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Viromi Fernando

    2014-01-01

    Full Text Available T helper (Th2 cells have been proposed to play a neuroprotective role in multiple sclerosis (MS. This is mainly based on “loss-of-function” studies in an animal model for MS, experimental autoimmune encephalomyelitis (EAE, using blocking antibodies against Th2 related cytokines, and knockout mice lacking Th2-related molecules. We tested whether an increase of Th2 responses (“gain-of-function” approach could alter EAE, the approach of novel GATA binding protein 3 (GATA3-transgenic (tg mice that overexpress GATA3, a transcription factor required for Th2 differentiation. In EAE induced with myelin oligodendrocyte glycoprotein (MOG35−55 peptide, GATA3-tg mice had a significantly delayed onset of disease and a less severe maximum clinical score, compared with wild-type C57BL/6 mice. Histologically, GATA3-tg mice had decreased levels of meningitis and demyelination in the spinal cord, and anti-inflammatory cytokine profiles immunologically, however both groups developed similar levels of MOG-specific lymphoproliferative responses. During the early stage, we detected higher levels of interleukin (IL-4 and IL-10, with MOG and mitogen stimulation of regional lymph node cells in GATA3-tg mice. During the late stage, only mitogen stimulation induced higher IL-4 and lower interferon-γ and IL-17 production in GATA3-tg mice. These results suggest that a preexisting bias toward a Th2 immune response may reduce the severity of inflammatory demyelinating diseases, including MS.

  1. Multiple complexes of nitrogen assimilatory enzymes in spinach chloroplasts: possible mechanisms for the regulation of enzyme function.

    Directory of Open Access Journals (Sweden)

    Yoko Kimata-Ariga

    Full Text Available Assimilation of nitrogen is an essential biological process for plant growth and productivity. Here we show that three chloroplast enzymes involved in nitrogen assimilation, glutamate synthase (GOGAT, nitrite reductase (NiR and glutamine synthetase (GS, separately assemble into distinct protein complexes in spinach chloroplasts, as analyzed by western blots under blue native electrophoresis (BN-PAGE. GOGAT and NiR were present not only as monomers, but also as novel complexes with a discrete size (730 kDa and multiple sizes (>120 kDa, respectively, in the stromal fraction of chloroplasts. These complexes showed the same mobility as each monomer on two-dimensional (2D SDS-PAGE after BN-PAGE. The 730 kDa complex containing GOGAT dissociated into monomers, and multiple complexes of NiR reversibly converted into monomers, in response to the changes in the pH of the stromal solvent. On the other hand, the bands detected by anti-GS antibody were present not only in stroma as a conventional decameric holoenzyme complex of 420 kDa, but also in thylakoids as a novel complex of 560 kDa. The polypeptide in the 560 kDa complex showed slower mobility than that of the 420 kDa complex on the 2D SDS-PAGE, implying the assembly of distinct GS isoforms or a post-translational modification of the same GS protein. The function of these multiple complexes was evaluated by in-gel GS activity under native conditions and by the binding ability of NiR and GOGAT with their physiological electron donor, ferredoxin. The results indicate that these multiplicities in size and localization of the three nitrogen assimilatory enzymes may be involved in the physiological regulation of their enzyme function, in a similar way as recently described cases of carbon assimilatory enzymes.

  2. Whole-body MRI, dynamic contrast-enhanced MRI, and diffusion-weighted imaging for the staging of multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Dutoit, Julie C.; Verstraete, Koenraad L. [Ghent University Hospital, Department of Radiology, Ghent (Belgium)

    2017-06-15

    Magnetic resonance imaging (MRI) is the most sensitive imaging technique for the detection of bone marrow infiltration, and has therefore recently been included in the new diagnostic myeloma criteria, as proposed by the International Myeloma Working Group. Nevertheless, conventional MRI only provides anatomical information and is therefore only of limited use in the response assessment of patients with multiple myeloma. The additional information from functional MRI techniques, such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, can improve the detection rate of bone marrow infiltration and the assessment of response. This can further enhance the sensitivity and specificity of MRI in the staging of multiple myeloma patients. This article provides an overview of the technical aspects of conventional and functional MRI techniques with practical recommendations. It reviews the diagnostic performance, prognostic value, and role in therapy assessment in multiple myeloma and its precursor stages. (orig.)

  3. Model of the regulation of the rate of multiplication of the stem cells of the bone marrow. [X radiation, gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gruzdev, G P; Monichev, A Ya

    1975-01-01

    A mathematical model of regulation of the rate of multiplication of the stem cells of the bone marrow has been constructed and investigated. Two possible variants of regulation of the proliferative activity of the irradiated stem cells are compared: at the level of tissue and subtissue units. Comparison of the results of modeling with the results of experimental investigations supports the latter mechanism of regulation of the proliferation of the stem cells.

  4. Multiple cone pathways are involved in photic regulation of retinal dopamine.

    Science.gov (United States)

    Qiao, Sheng-Nan; Zhang, Zhijing; Ribelayga, Christophe P; Zhong, Yong-Mei; Zhang, Dao-Qi

    2016-06-30

    Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system. The sole source of retinal dopamine is dopaminergic amacrine cells (DACs). We and others have previously demonstrated that DACs are activated by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) upon illumination. However, it is still not clear how each class of photosensitive cells generates light responses in DACs. We genetically isolated cone function in mice to specifically examine the cone-mediated responses of DACs and their neural pathways. In addition to the reported excitatory input to DACs from light-increment (ON) bipolar cells, we found that cones alternatively signal to DACs via a retrograde signalling pathway from ipRGCs. Cones also produce ON and light-decrement (OFF) inhibitory responses in DACs, which are mediated by other amacrine cells, likely driven by type 1 and type 2/3a OFF bipolar cells, respectively. Dye injections indicated that DACs had similar morphological profiles with or without ON/OFF inhibition. Our data demonstrate that cones utilize specific parallel excitatory and inhibitory circuits to modulate DAC activity and efficiently regulate dopamine release and the light-adaptive state of the retina.

  5. Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance.

    Science.gov (United States)

    Dellett, Margaret; Hu, Wanzhou; Papadaki, Vasiliki; Ohnuma, Shin-ichi

    2012-04-01

    The small leucine-rich repeat proteoglycan (SLRPs) family of proteins currently consists of five classes, based on their structural composition and chromosomal location. As biologically active components of the extracellular matrix (ECM), SLRPs were known to bind to various collagens, having a role in regulating fibril assembly, organization and degradation. More recently, as a function of their diverse proteins cores and glycosaminoglycan side chains, SLRPs have been shown to be able to bind various cell surface receptors, growth factors, cytokines and other ECM components resulting in the ability to influence various cellular functions. Their involvement in several signaling pathways such as Wnt, transforming growth factor-β and epidermal growth factor receptor also highlights their role as matricellular proteins. SLRP family members are expressed during neural development and in adult neural tissues, including ocular tissues. This review focuses on describing SLRP family members involvement in neural development with a brief summary of their role in non-neural ocular tissues and in response to neural injury. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

  6. Multiple structure-intrinsic disorder interactions regulate and coordinate Hox protein function

    Science.gov (United States)

    Bondos, Sarah

    During animal development, Hox transcription factors determine fate of developing tissues to generate diverse organs and appendages. Hox proteins are famous for their bizarre mutant phenotypes, such as replacing antennae with legs. Clearly, the functions of individual Hox proteins must be distinct and reliable in vivo, or the organism risks malformation or death. However, within the Hox protein family, the DNA-binding homeodomains are highly conserved and the amino acids that contact DNA are nearly invariant. These observations raise the question: How do different Hox proteins correctly identify their distinct target genes using a common DNA binding domain? One possible means to modulate DNA binding is through the influence of the non-homeodomain protein regions, which differ significantly among Hox proteins. However genetic approaches never detected intra-protein interactions, and early biochemical attempts were hindered because the special features of ``intrinsically disordered'' sequences were not appreciated. We propose the first-ever structural model of a Hox protein to explain how specific contacts between distant, intrinsically disordered regions of the protein and the homeodomain regulate DNA binding and coordinate this activity with other Hox molecular functions.

  7. Novel energy-saving strategies to multiple stressors in birds: the ultradian regulation of body temperature.

    Science.gov (United States)

    Tattersall, Glenn J; Roussel, Damien; Voituron, Yann; Teulier, Loïc

    2016-09-28

    This study aimed to examine thermoregulatory responses in birds facing two commonly experienced stressors, cold and fasting. Logging devices allowing long-term and precise access to internal body temperature were placed within the gizzards of ducklings acclimated to cold (CA) (5°C) or thermoneutrality (TN) (25°C). The animals were then examined under three equal 4-day periods: ad libitum feeding, fasting and re-feeding. Through the analysis of daily as well as short-term, or ultradian, variations of body temperature, we showed that while ducklings at TN show only a modest decline in daily thermoregulatory parameters when fasted, they exhibit reduced surface temperatures from key sites of vascular heat exchange during fasting. The CA birds, on the other hand, significantly reduced their short-term variations of body temperature while increasing long-term variability when fasting. This phenomenon would allow the CA birds to reduce the energetic cost of body temperature maintenance under fasting. By analysing ultradian regulation of body temperature, we describe a means by which an endotherm appears to lower thermoregulatory costs in response to the combined stressors of cold and fasting. © 2016 The Author(s).

  8. Dynamic analysis of multiple nuclear-coupled boiling channels based on a multi-point reactor model

    International Nuclear Information System (INIS)

    Lee, J.D.; Pan Chin

    2005-01-01

    This work investigates the non-linear dynamics and stabilities of a multiple nuclear-coupled boiling channel system based on a multi-point reactor model using the Galerkin nodal approximation method. The nodal approximation method for the multiple boiling channels developed by Lee and Pan [Lee, J.D., Pan, C., 1999. Dynamics of multiple parallel boiling channel systems with forced flows. Nucl. Eng. Des. 192, 31-44] is extended to address the two-phase flow dynamics in the present study. The multi-point reactor model, modified from Uehiro et al. [Uehiro, M., Rao, Y.F., Fukuda, K., 1996. Linear stability analysis on instabilities of in-phase and out-of-phase modes in boiling water reactors. J. Nucl. Sci. Technol. 33, 628-635], is employed to study a multiple-channel system with unequal steady-state neutron density distribution. Stability maps, non-linear dynamics and effects of major parameters on the multiple nuclear-coupled boiling channel system subject to a constant total flow rate are examined. This study finds that the void-reactivity feedback and neutron interactions among subcores are coupled and their competing effects may influence the system stability under different operating conditions. For those cases with strong neutron interaction conditions, by strengthening the void-reactivity feedback, the nuclear-coupled effect on the non-linear dynamics may induce two unstable oscillation modes, the supercritical Hopf bifurcation and the subcritical Hopf bifurcation. Moreover, for those cases with weak neutron interactions, by quadrupling the void-reactivity feedback coefficient, period-doubling and complex chaotic oscillations may appear in a three-channel system under some specific operating conditions. A unique type of complex chaotic attractor may evolve from the Rossler attractor because of the coupled channel-to-channel thermal-hydraulic and subcore-to-subcore neutron interactions. Such a complex chaotic attractor has the imbedding dimension of 5 and the

  9. REGULATION OF EXPRESSION OF MULTIPLE BETA- GLUCOSIDASES OF ASPERGILLUS TERREUS AND THEIR PURIFICATION AND CHARACTERIZATION

    Directory of Open Access Journals (Sweden)

    Asiya Nazir

    2009-02-01

    Full Text Available This study reports the regulation and purification of -glucosidases from a thermotolerant Aspergillus terreus AN1 strain, previously reported for efficient deinking of composite paper waste. The differential expression of four -glucosidase isoforms, in response to carbon sources in production medium, was studied by electrophoretically resolving proteins by polyacrylamide gel electro-phoresis analysis (PAGE and developing zymograms using methylum-belliferyl -D glucoside as substrate. Three -glucosidases (GI, GII & GIII were purified using chromatographic techniques. SDS-PAGE revealed the respective molecular masses of GI, GII, and GIII, as 29, 43, and 98 KDa, and isoelectric point (pI to be 2.8, 3.7, and 3.0. The -glucosidases exhibited diverse pH and temperature optima as well as stability. -Glucosidase I (GI specifically recog-nized pNP--glucopyranoside (pNPG as a substrate, whereas, -glucosidase II (GII and III (GIII also showed activities against cellobiose and salicin. In contrast to GII and GIII, the activity of GI was positively influenced in the presence of hexoses/pentoses and alcohols. Km and Vmax for hydrolysis of pNPG by GI, GII, andGIII were found to be 14.2 mM and 166.9 µmol -1mg protein -1, 4.37 mM, and 34.7 µmol -1mg proteins -1, and 11.1 mM and 378.7µ mol -1 mg protein -1, respectively.

  10. INFORMATION MINING OF SPATIO-TEMPORAL EVOLUTION OF LAKES BASED ON MULTIPLE DYNAMIC MEASUREMENTS

    Directory of Open Access Journals (Sweden)

    W. Feng

    2017-09-01

    Full Text Available Lakes are important water resources and integral parts of the natural ecosystem, and it is of great significance to study the evolution of lakes. The area of each lake increased and decreased at the same time in natural condition, only but the net change of lakes’ area is the result of the bidirectional evolution of lakes. In this paper, considering the effects of net fragmentation, net attenuation, swap change and spatial invariant part in lake evolution, a comprehensive evaluation indexes of lake dynamic evolution were defined,. Such degree contains three levels of measurement: 1 the swap dynamic degree (SDD reflects the space activity of lakes in the study period. 2 the attenuation dynamic degree (ADD reflects the net attenuation of lakes into non-lake areas. 3 the fragmentation dynamic degree (FDD reflects the trend of lakes to be divided and broken into smaller lakes. Three levels of dynamic measurement constitute the three-dimensional "Swap - attenuation – fragmentation" dynamic evolution measurement system of lakes. To show its effectiveness, the dynamic measurement was applied to lakes in Jianghan Plain, the middle Yangtze region of China for a more detailed analysis of lakes from 1984 to 2014. In combination with spatial-temporal location characteristics of lakes, the hidden information in lake evolution in the past 30 years can be revealed.

  11. Functional Dynamics within the Human Ribosome Regulate the Rate of Active Protein Synthesis.

    Science.gov (United States)

    Ferguson, Angelica; Wang, Leyi; Altman, Roger B; Terry, Daniel S; Juette, Manuel F; Burnett, Benjamin J; Alejo, Jose L; Dass, Randall A; Parks, Matthew M; Vincent, C Theresa; Blanchard, Scott C

    2015-11-05

    The regulation of protein synthesis contributes to gene expression in both normal physiology and disease, yet kinetic investigations of the human translation mechanism are currently lacking. Using single-molecule fluorescence imaging methods, we have quantified the nature and timing of structural processes in human ribosomes during single-turnover and processive translation reactions. These measurements reveal that functional complexes exhibit dynamic behaviors and thermodynamic stabilities distinct from those observed for bacterial systems. Structurally defined sub-states of pre- and post-translocation complexes were sensitive to specific inhibitors of the eukaryotic ribosome, demonstrating the utility of this platform to probe drug mechanism. The application of three-color single-molecule fluorescence resonance energy transfer (smFRET) methods further revealed a long-distance allosteric coupling between distal tRNA binding sites within ribosomes bearing three tRNAs, which contributed to the rate of processive translation. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Multiple Reserve Requirements, Exchange Rates, Sudden Stops and Equilibrium Dynamics in a Small Open Economy

    OpenAIRE

    Paula Hernandez-Verme; Wen-Yao Wang

    2009-01-01

    We model a typical Asian-crisis-economy using dynamic general equilibrium tech-niques. Exchange rates obtain from nontrivial fiat-currencies demands. Sudden stops/bank-panics are possible, and key for evaluating the merits of alternative ex-change rate regimes. Strategic complementarities contribute to the severe indetermi-nacy of the continuum of equilibria. The scope for existence and indeterminacy of equilibria and dynamic properties are associated with the underlying policy regime. Bindin...

  13. Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly.

    Science.gov (United States)

    Yeo, Giselle C; Tarakanova, Anna; Baldock, Clair; Wise, Steven G; Buehler, Markus J; Weiss, Anthony S

    2016-02-01

    The assembly of the tropoelastin monomer into elastin is vital for conferring elasticity on blood vessels, skin, and lungs. Tropoelastin has dual needs for flexibility and structure in self-assembly. We explore the structure-dynamics-function interplay, consider the duality of molecular order and disorder, and identify equally significant functional contributions by local and global structures. To study these organizational stratifications, we perturb a key hinge region by expressing an exon that is universally spliced out in human tropoelastins. We find a herniated nanostructure with a displaced C terminus and explain by molecular modeling that flexible helices are replaced with substantial β sheets. We see atypical higher-order cross-linking and inefficient assembly into discontinuous, thick elastic fibers. We explain this dysfunction by correlating local and global structural effects with changes in the molecule's assembly dynamics. This work has general implications for our understanding of elastomeric proteins, which balance disordered regions with defined structural modules at multiple scales for functional assembly.

  14. Recent research and applications of numerical simulation for dynamic response of long-span bridges subjected to multiple loads.

    Science.gov (United States)

    Chen, Zhiwei; Chen, Bo

    2014-01-01

    Many long-span bridges have been built throughout the world in recent years but they are often subject to multiple types of dynamic loads, especially those located in wind-prone regions and carrying both trains and road vehicles. To ensure the safety and functionality of these bridges, dynamic responses of long-span bridges are often required for bridge assessment. Given that there are several limitations for the assessment based on field measurement of dynamic responses, a promising approach is based on numerical simulation technologies. This paper provides a detailed review of key issues involved in dynamic response analysis of long-span multiload bridges based on numerical simulation technologies, including dynamic interactions between running trains and bridge, between running road vehicles and bridge, and between wind and bridge, and in the wind-vehicle-bridge coupled system. Then a comprehensive review is conducted for engineering applications of newly developed numerical simulation technologies to safety assessment of long-span bridges, such as assessment of fatigue damage and assessment under extreme events. Finally, the existing problems and promising research efforts for the numerical simulation technologies and their applications to assessment of long-span multiload bridges are explored.

  15. Regulation of ER-Golgi Transport Dynamics by GTPases in Budding Yeast

    Directory of Open Access Journals (Sweden)

    Yasuyuki Suda

    2018-01-01

    Full Text Available A large number of proteins are synthesized de novo in the endoplasmic reticulum (ER. They are transported through the Golgi apparatus and then delivered to their proper destinations. The ER and the Golgi play a central role in protein processing and sorting and show dynamic features in their forms. Ras super family small GTPases mediate the protein transport through and between these organelles. The ER-localized GTPase, Sar1, facilitates the formation of COPII transport carriers at the ER exit sites (ERES on the ER for the transport of cargo proteins from the ER to the Golgi. The Golgi-localized GTPase, Arf1, controls intra-Golgi, and Golgi-to-ER transport of cargo proteins by the formation of COPI carriers. Rab GTPases localized at the Golgi, which are responsible for fusion of membranes, are thought to establish the identities of compartments. Recent evidence suggests that these small GTPases regulate not only discrete sites for generation/fusion of transport carriers, but also membrane dynamics of the organelles where they locate to ensure the integrity of transport. Here we summarize the current understandings about the membrane traffic between these organelles and highlight the cutting-edge advances from super-resolution live imaging of budding yeast, Saccharomyces cerevisiae.

  16. Nontranscriptional regulation of SYK by the coactivator OCA-B is required at multiple stages of B cell development.

    Science.gov (United States)

    Siegel, Rachael; Kim, Unkyu; Patke, Alina; Yu, Xin; Ren, Xiaodi; Tarakhovsky, Alexander; Roeder, Robert G

    2006-05-19

    OCA-B was originally identified as a nuclear transcriptional coactivator that is essential for antigen-driven immune responses. The later identification of a membrane bound, myristoylated form of OCA-B suggested additional, unique functions in B cell signaling pathways. This study has shown that OCA-B also functions in the pre-B1-to-pre-B2 cell transition and, most surprisingly, that it directly interacts with SYK, a tyrosine kinase critical for pre-BCR and BCR signaling. This unprecedented type of interaction-a transcriptional coactivator with a signaling kinase-occurs in the cytoplasm and directly regulates SYK stability. This study indicates that OCA-B is required for pre-BCR and BCR signaling at multiple stages of B cell development through its nontranscriptional regulation of SYK. Combined with the deregulation of OCA-B target genes, this may help explain the multitude of defects observed in B cell development and immune responses of Oca-b-/- mice.

  17. Impacts of small scale flow regulation on sediment dynamics in an ecologically important upland river.

    Science.gov (United States)

    Quinlan, E; Gibbins, C N; Batalla, R J; Vericat, D

    2015-03-01

    Flow regulation is widely recognized as affecting fluvial processes and river ecosystems. Most impact assessments have focused on large dams and major water transfer schemes, so relatively little is known about the impacts of smaller dams, weirs and water diversions. This paper assesses sediment dynamics in an upland river (the Ehen, NW England) whose flows are regulated by a small weir and tributary diversion. The river is important ecologically due to the presence of the endangered freshwater pearl mussel Margaritifera margaritifera, a species known to be sensitive to sedimentary conditions. Fine sediment yield for the 300-m long study reach was estimated to be 0.057 t km(-2) year(-1), a very low value relative to other upland UK rivers. Mean in-channel storage of fine sediment was also low, estimated at an average of around 40 g m(-2). Although the study period was characterized by frequent high flow events, little movement of coarser bed material was observed. Data therefore indicate an extremely stable fluvial system within the study reach. The implication of this stability for pearl mussels is discussed.

  18. Ornithine decarboxylase and extracellular polyamines regulate microvascular sprouting and actin cytoskeleton dynamics in endothelial cells

    International Nuclear Information System (INIS)

    Kucharzewska, Paulina; Welch, Johanna E.; Svensson, Katrin J.; Belting, Mattias

    2010-01-01

    The polyamines are essential for cancer cell proliferation during tumorigenesis. Targeted inhibition of ornithine decarboxylase (ODC), i.e. a key enzyme of polyamine biosynthesis, by α-difluoromethylornithine (DFMO) has shown anti-neoplastic activity in various experimental models. This activity has mainly been attributed to the anti-proliferative effect of DFMO in cancer cells. Here, we provide evidence that unperturbed ODC activity is a requirement for proper microvessel sprouting ex vivo as well as the migration of primary human endothelial cells. DFMO-mediated ODC inhibition was reversed by extracellular polyamine supplementation, showing that anti-angiogenic effects of DFMO were specifically related to polyamine levels. ODC inhibition was associated with an abnormal morphology of the actin cytoskeleton during cell spreading and migration. Moreover, our data suggest that de-regulated actin cytoskeleton dynamics in DFMO treated endothelial cells may be related to constitutive activation of the small GTPase CDC42, i.e. a well-known regulator of cell motility and actin cytoskeleton remodeling. These insights into the potential role of polyamines in angiogenesis should stimulate further studies testing the combined anti-tumor effect of polyamine inhibition and established anti-angiogenic therapies in vivo.

  19. Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

    Science.gov (United States)

    Kagawa, Yoshinori; Matsumoto, Shinji; Kamioka, Yuji; Mimori, Koshi; Naito, Yoko; Ishii, Taeko; Okuzaki, Daisuke; Nishida, Naohiro; Maeda, Sakae; Naito, Atsushi; Kikuta, Junichi; Nishikawa, Keizo; Nishimura, Junichi; Haraguchi, Naotsugu; Takemasa, Ichiro; Mizushima, Tsunekazu; Ikeda, Masataka; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Ishii, Hideshi; Doki, Yuichiro; Matsuda, Michiyuki; Kikuchi, Akira; Mori, Masaki; Ishii, Masaru

    2013-01-01

    The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

  20. Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

    Directory of Open Access Journals (Sweden)

    Yoshinori Kagawa

    Full Text Available The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP, was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

  1. The Treg/Th17 axis: A dynamic balance regulated by the gut microbiome

    Directory of Open Access Journals (Sweden)

    Sara eOmenetti

    2015-12-01

    Full Text Available T-helper 17 (Th17 and T-regulatory (Treg cells are frequently found at barrier surfaces, particularly within the intestinal mucosa, where they function to protect the host from pathogenic microorganisms and to restrain excessive effector T-cell responses, respectively. Despite their differing functional properties, Th17 cells and Tregs share similar developmental requirements. In fact, the fate of antigen-naïve T-cells to either Th17 or Treg lineages is finely regulated by key mediators, including TGFβ, IL-6 and all-trans retinoic acid (RA. Importantly, the intestinal microbiome also provides immunostimulatory signals, which can activate innate, and downstream adaptive, immune responses. Specific components of the gut microbiome have been implicated in the production of proinflammatory cytokines by innate immune cells, such as IL-6, IL-23, IL-1β, and the subsequent generation and expansion of Th17 cells. Similarly, commensal bacteria and their metabolites can also promote the generation of intestinal Tregs that can actively induce mucosal tolerance. As such, dysbiosis of the gut microbiome may not solely represent a consequence of gut inflammation, but rather shape the Treg/Th17 commitment and influence susceptibility to inflammatory bowel disease (IBD. In this review, we discuss Treg and Th17 cell plasticity, its dynamic regulation by the microbiome, and highlight its impact on intestinal homeostasis and disease.

  2. Laccase-13 Regulates Seed Setting Rate by Affecting Hydrogen Peroxide Dynamics and Mitochondrial Integrity in Rice

    Directory of Open Access Journals (Sweden)

    Yang Yu

    2017-07-01

    Full Text Available Seed setting rate is one of the most important components of rice grain yield. To date, only several genes regulating setting rate have been identified in plant. In this study, we showed that laccase-13 (OsLAC13, a member of laccase family genes which are known for their roles in modulating phenylpropanoid pathway and secondary lignification in cell wall, exerts a regulatory function in rice seed setting rate. OsLAC13 expressed in anthers and promotes hydrogen peroxide production both in vitro and in the filaments and anther connectives. Knock-out of OsLAC13 showed significantly increased seed setting rate, while overexpression of this gene exhibited induced mitochondrial damage and suppressed sugar transportation in anthers, which in turn affected seed setting rate. OsLAC13 also induced H2O2 production and mitochondrial damage in the root tip cells which caused the lethal phenotype. We also showed that high abundant of OsmiR397, the suppressor of OsLAC13 mRNA, increased the seed setting rate of rice plants, and restrains H2O2 accumulation in roots during oxidative stress. Our results suggested a novel regulatory role of OsLAC13 gene in regulating seed setting rate by affecting H2O2 dynamics and mitochondrial integrity in rice.

  3. In Vitro Effect of Malachite Green on Candida albicans Involves Multiple Pathways and Transcriptional Regulators UPC2 and STP2

    Science.gov (United States)

    Dhamgaye, Sanjiveeni; Devaux, Frederic; Manoharlal, Raman; Vandeputte, Patrick; Shah, Abdul Haseeb; Singh, Ashutosh; Blugeon, Corinne; Sanglard, Dominique

    2012-01-01

    In this study, we show that a chemical dye, malachite green (MG), which is commonly used in the fish industry as an antifungal, antiparasitic, and antibacterial agent, could effectively kill Candida albicans and non-C. albicans species. We have demonstrated that Candida cells are susceptible to MG at a very low concentration (MIC that reduces growth by 50% [MIC50], 100 ng ml−1) and that the effect of MG is independent of known antifungal targets, such as ergosterol metabolism and major drug efflux pump proteins. Transcriptional profiling in response to MG treatment of C. albicans cells revealed that of a total of 207 responsive genes, 167 genes involved in oxidative stress, virulence, carbohydrate metabolism, heat shock, amino acid metabolism, etc., were upregulated, while 37 genes involved in iron acquisition, filamentous growth, mitochondrial respiration, etc., were downregulated. We confirmed experimentally that Candida cells exposed to MG resort to a fermentative mode of metabolism, perhaps due to defective respiration. In addition, we showed that MG triggers depletion of intracellular iron pools and enhances reactive oxygen species (ROS) levels. These effects could be reversed by the addition of iron or antioxidants, respectively. We provided evidence that the antifungal effect of MG is exerted through the transcription regulators UPC2 (regulating ergosterol biosynthesis and azole resistance) and STP2 (regulating amino acid permease genes). Taken together, our transcriptome, genetic, and biochemical results allowed us to decipher the multiple mechanisms by which MG exerts its anti-Candida effects, leading to a metabolic shift toward fermentation, increased generation of ROS, labile iron deprivation, and cell necrosis. PMID:22006003

  4. Connections Between Future Time Perspectives and Self-Regulated Learning for Mid-Year Engineering Students: A Multiple Case Study

    Science.gov (United States)

    Chasmar, Justine

    This dissertation presents multiple studies with the purpose of understanding the connections between undergraduate engineering students' motivations, specifically students' Future Time Perspectives (FTPs) and Self-Regulated Learning (SRL). FTP refers to the views students hold about the future and how their perceptions of current tasks are affected by these views. SRL connects the behaviors, metacognition, and motivation of students in their learning. The goals of this research project were to 1) qualitatively describe and document engineering students' SRL strategies, 2) examine interactions between engineering students' FTPs and SRL strategy use, and 3) explore goal-setting as a bridge between FTP and SRL. In an exploratory qualitative study with mid-year industrial engineering students to examine the SRL strategies used before and after an SRL intervention, results showed that students intended to use more SRL strategies than they attempted. However, students self-reported using new SRL strategies from the intervention. Students in this population also completed a survey and a single interview about FTP and SRL. Results showed perceptions of instrumentality of coursework and skills as motivation for using SRL strategies, and a varied use of SRL strategies for students with different FTPs. Overall, three types of student FTP were seen: students with a single realistic view of the future, conflicting ideal and realistic future views, or open views of the future. A sequential explanatory mixed methods study was conducted with mid-year students from multiple engineering majors. First a cluster analysis of survey results of FTP items compared to FTP interview responses was used for participant selection. Then a multiple case study was conducted with data collected through surveys, journal entries, course performance, and two interviews. Results showed that students with a well-defined FTP self-regulated in the present based on their varied perceptions of

  5. Autonomous and controlled motivational regulations for multiple health-related behaviors: between- and within-participants analyses

    Science.gov (United States)

    Hagger, M.S.; Hardcastle, S.J.; Chater, A.; Mallett, C.; Pal, S.; Chatzisarantis, N.L.D.

    2014-01-01

    Self-determination theory has been applied to the prediction of a number of health-related behaviors with self-determined or autonomous forms of motivation generally more effective in predicting health behavior than non-self-determined or controlled forms. Research has been confined to examining the motivational predictors in single health behaviors rather than comparing effects across multiple behaviors. The present study addressed this gap in the literature by testing the relative contribution of autonomous and controlling motivation to the prediction of a large number of health-related behaviors, and examining individual differences in self-determined motivation as a moderator of the effects of autonomous and controlling motivation on health behavior. Participants were undergraduate students (N = 140) who completed measures of autonomous and controlled motivational regulations and behavioral intention for 20 health-related behaviors at an initial occasion with follow-up behavioral measures taken four weeks later. Path analysis was used to test a process model for each behavior in which motivational regulations predicted behavior mediated by intentions. Some minor idiosyncratic findings aside, between-participants analyses revealed significant effects for autonomous motivational regulations on intentions and behavior across the 20 behaviors. Effects for controlled motivation on intentions and behavior were relatively modest by comparison. Intentions mediated the effect of autonomous motivation on behavior. Within-participants analyses were used to segregate the sample into individuals who based their intentions on autonomous motivation (autonomy-oriented) and controlled motivation (control-oriented). Replicating the between-participants path analyses for the process model in the autonomy- and control-oriented samples did not alter the relative effects of the motivational orientations on intention and behavior. Results provide evidence for consistent effects

  6. Thermal effects in the hadronic and photonic multiplicity distributions and correlations: a thermo-field dynamic approach

    International Nuclear Information System (INIS)

    Bambah, Bindu A.; Mogurampally, Naveen Kumar

    2016-01-01

    The existence of the Quark Gluon Plasma (QGP) requires that in the collision of heavy ions an initial fireball is formed which has a lifetime larger than typical hadronic time scale of 10"−"2"3 sec and that the temperature and volume of the fireball is sufficient to ensure that the Quark Hadron phase transition predicted by statistical QCD is achieved. Then the pions and photons emitted from this hot fire ball may carry information of the temperature and life time of the emitting region, and this may manifest itself in the correlation functions and multiplicities which can be modified by finite temperature. Thus it is important to find ways of incorporating finite temperature effects in multiplicity distributions and correlations. The Thermo field formalism is particularly useful in the description of parametric dynamical systems in which squeezing of quantum fluctuations is important

  7. Ultrafast carrier dynamics in InGaN/GaN multiple quantum wells

    DEFF Research Database (Denmark)

    Porte, Henrik; Turchinovich, Dmitry; Cooke, David

    We studied the THz conductivity of InGaN/GaN multiple quantum wells (MQWs)by time-resolved terahertz spectroscopy. A nonexponential carrier density decay is observed due to the restoration of a built-in piezoelectric field. Terahertz conductivity spectra show a nonmetallic behavior of the carriers....

  8. Temporal brain dynamics of multiple object processing: the flexibility of individuation.

    Directory of Open Access Journals (Sweden)

    Veronica Mazza

    Full Text Available The ability to process concurrently multiple visual objects is fundamental for a coherent perception of the world. A core component of this ability is the simultaneous individuation of multiple objects. Many studies have addressed the mechanism of object individuation but it remains unknown whether the visual system mandatorily individuates all relevant elements in the visual field, or whether object indexing depends on task demands. We used a neural measure of visual selection, the N2pc component, to evaluate the flexibility of multiple object individuation. In three ERP experiments, participants saw a variable number of target elements among homogenous distracters and performed either an enumeration task (Experiment 1 or a detection task, reporting whether at least one (Experiment 2 or a specified number of target elements (Experiment 3 was present. While in the enumeration task the N2pc response increased as a function of the number of targets, no such modulation was found in Experiment 2, indicating that individuation of multiple targets is not mandatory. However, a modulation of the N2pc similar to the enumeration task was visible in Experiment 3, further highlighting that object individuation is a flexible mechanism that binds indexes to object properties and locations as needed for further object processing.

  9. Modeling complex effects of multiple environmental stresses on carbon dynamics of Mid-Atlantic temperate forests

    Science.gov (United States)

    Yude Pan; Richard Birdsey; John Hom; Kevin McCullough

    2007-01-01

    We used our GIS variant of the PnET-CN model to investigate changes of forest carbon stocks and fluxes in Mid-Atlantic temperate forests over the last century (1900-2000). Forests in this region are affected by multiple environmental changes including climate, atmospheric CO2 concentration, N deposition and tropospheric ozone, and extensive land disturbances. Our...

  10. Neural Dynamics Associated with Semantic and Episodic Memory for Faces: Evidence from Multiple Frequency Bands

    Science.gov (United States)

    Zion-Golumbic, Elana; Kutas, Marta; Bentin, Shlomo

    2010-01-01

    Prior semantic knowledge facilitates episodic recognition memory for faces. To examine the neural manifestation of the interplay between semantic and episodic memory, we investigated neuroelectric dynamics during the creation (study) and the retrieval (test) of episodic memories for famous and nonfamous faces. Episodic memory effects were evident…

  11. Probabilistic assessment of the dynamic interaction between multiple pedestrians and vertical vibrations of footbridges

    Science.gov (United States)

    Tubino, Federica

    2018-03-01

    The effect of human-structure interaction in the vertical direction for footbridges is studied based on a probabilistic approach. The bridge is modeled as a continuous dynamic system, while pedestrians are schematized as moving single-degree-of-freedom systems with random dynamic properties. The non-dimensional form of the equations of motion allows us to obtain results that can be applied in a very wide set of cases. An extensive Monte Carlo simulation campaign is performed, varying the main non-dimensional parameters identified, and the mean values and coefficients of variation of the damping ratio and of the non-dimensional natural frequency of the coupled system are reported. The results obtained can be interpreted from two different points of view. If the characterization of pedestrians' equivalent dynamic parameters is assumed as uncertain, as revealed from a current literature review, then the paper provides a range of possible variations of the coupled system damping ratio and natural frequency as a function of pedestrians' parameters. Assuming that a reliable characterization of pedestrians' dynamic parameters is available (which is not the case at present, but could be in the future), the results presented can be adopted to estimate the damping ratio and natural frequency of the coupled footbridge-pedestrian system for a very wide range of real structures.

  12. Mapping groundwater dynamics using multiple sources of exhaustive high resolution data

    NARCIS (Netherlands)

    Finke, P.A.; Brus, D.J.; Bierkens, M.F.P.; Hoogland, T.; Knotters, M.; Vries, de F.

    2004-01-01

    Existing groundwater table (GWT) class maps, available at full coverage for the Netherlands at 1:50,000 scale, no longer satisfy user demands. Groundwater levels have changed due to strong human impact, so the maps are partially outdated. Furthermore, a more dynamic description of groundwater table

  13. Structural dynamics of surfaces by ultrafast electron crystallography: experimental and multiple scattering theory.

    Science.gov (United States)

    Schäfer, Sascha; Liang, Wenxi; Zewail, Ahmed H

    2011-12-07

    Recent studies in ultrafast electron crystallography (UEC) using a reflection diffraction geometry have enabled the investigation of a wide range of phenomena on the femtosecond and picosecond time scales. In all these studies, the analysis of the diffraction patterns and their temporal change after excitation was performed within the kinematical scattering theory. In this contribution, we address the question, to what extent dynamical scattering effects have to be included in order to obtain quantitative information about structural dynamics. We discuss different scattering regimes and provide diffraction maps that describe all essential features of scatterings and observables. The effects are quantified by dynamical scattering simulations and examined by direct comparison to the results of ultrafast electron diffraction experiments on an in situ prepared Ni(100) surface, for which structural dynamics can be well described by a two-temperature model. We also report calculations for graphite surfaces. The theoretical framework provided here allows for further UEC studies of surfaces especially at larger penetration depths and for those of heavy-atom materials. © 2011 American Institute of Physics

  14. Dynamics and waves near multiple magnetic null points in reconnection diffusion region

    Czech Academy of Sciences Publication Activity Database

    Deng, X. H.; Zhou, M.; Li, S. Y.; Baumjohann, W.; Andre, M.; Cornilleau, N.; Santolík, Ondřej; Pontin, D. I.; Reme, H.; Lucek, E.; Fazakerley, A. N.; Decreau, P.; Daly, P.; Nakamura, R.; Tang, R. X.; Hu, Y. H.; Pang, Y.; Büchner, J.; Zhao, H.; Vaivads, A.; Pickett, J. S.; Ng, C. S.; Lin, X.; Fu, S.; Yuan, Z. G.; Su, Z. W.; Wang, J. F.

    2009-01-01

    Roč. 114, - (2009), A07216/1-A07216/7 ISSN 0148-0227 Institutional research plan: CEZ:AV0Z30420517 Keywords : waves * dynamics * reconnection * diffusion Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 3.082, year: 2009

  15. Fungible dynamics: There are only two types of entangling multiple-qubit interactions

    International Nuclear Information System (INIS)

    Bremner, Michael J.; Dodd, Jennifer L.; Nielsen, Michael A.; Bacon, Dave

    2004-01-01

    What interactions are sufficient to simulate arbitrary quantum dynamics in a composite quantum system? It has been shown that all two-body Hamiltonian evolutions can be simulated using any fixed two-body entangling n-qubit Hamiltonian and fast local unitaries. By entangling we mean that every qubit is coupled to every other qubit, if not directly, then indirectly via intermediate qubits. We extend this study to the case where interactions may involve more than two qubits at a time. We find necessary and sufficient conditions for an arbitrary n-qubit Hamiltonian to be dynamically universal, that is, able to simulate any other Hamiltonian acting on n qubits, possibly in an inefficient manner. We prove that an entangling Hamiltonian is dynamically universal if and only if it contains at least one coupling term involving an even number of interacting qubits. For odd entangling Hamiltonians, i.e., Hamiltonians with couplings that involve only an odd number of qubits, we prove that dynamic universality is possible on an encoded set of n-1 logical qubits. We further prove that an odd entangling Hamiltonian can simulate any other odd Hamiltonian and classify the algebras that such Hamiltonians generate. Thus, our results show that up to local unitary operations, there are only two fundamentally different types of entangling Hamiltonian on n qubits. We also demonstrate that, provided the number of qubits directly coupled by the Hamiltonian is bounded above by a constant, our techniques can be made efficient

  16. Influence of Multiple Infection and Relatedness on Virulence: Disease Dynamics in an Experimental Plant Population and Its Castrating Parasite

    Science.gov (United States)

    Buono, Lorenza; López-Villavicencio, Manuela; Shykoff, Jacqui A.; Snirc, Alodie; Giraud, Tatiana

    2014-01-01

    The level of parasite virulence, i.e., the decrease in host's fitness due to a pathogen, is expected to depend on several parameters, such as the type of the disease (e.g., castrating or host-killing) and the prevalence of multiple infections. Although these parameters have been extensively studied theoretically, few empirical data are available to validate theoretical predictions. Using the anther smut castrating disease on Silene latifolia caused by Microbotryum lychnidis-dioicae, we studied the dynamics of multiple infections and of different components of virulence (host death, non-recovery and percentage of castrated stems) during the entire lifespan of the host in an experimental population. We monitored the number of fungal genotypes within plants and their relatedness across five years, using microsatellite markers, as well as the rates of recovery and host death in the population. The mean relatedness among genotypes within plants remained at a high level throughout the entire host lifespan despite the dynamics of the disease, with recurrent new infections. Recovery was lower for plants with multiple infections compared to plants infected by a single genotype. As expected for castrating parasites, M. lychnidis-dioicae did not increase host mortality. Mortality varied across years but was generally lower for plants that had been diseased the preceding year. This is one of the few studies to have empirically verified theoretical expectations for castrating parasites, and to show particularly i) that castrated hosts live longer, suggesting that parasites can redirect resources normally used in reproduction to increase host lifespan, lengthening their transmission phase, and ii) that multiple infections increase virulence, here in terms of non-recovery and host castration. PMID:24892951

  17. Nonadiabatic dynamics of electron transfer in solution: Explicit and implicit solvent treatments that include multiple relaxation time scales

    International Nuclear Information System (INIS)

    Schwerdtfeger, Christine A.; Soudackov, Alexander V.; Hammes-Schiffer, Sharon

    2014-01-01

    The development of efficient theoretical methods for describing electron transfer (ET) reactions in condensed phases is important for a variety of chemical and biological applications. Previously, dynamical dielectric continuum theory was used to derive Langevin equations for a single collective solvent coordinate describing ET in a polar solvent. In this theory, the parameters are directly related to the physical properties of the system and can be determined from experimental data or explicit molecular dynamics simulations. Herein, we combine these Langevin equations with surface hopping nonadiabatic dynamics methods to calculate the rate constants for thermal ET reactions in polar solvents for a wide range of electronic couplings and reaction free energies. Comparison of explicit and implicit solvent calculations illustrates that the mapping from explicit to implicit solvent models is valid even for solvents exhibiting complex relaxation behavior with multiple relaxation time scales and a short-time inertial response. The rate constants calculated for implicit solvent models with a single solvent relaxation time scale corresponding to water, acetonitrile, and methanol agree well with analytical theories in the Golden rule and solvent-controlled regimes, as well as in the intermediate regime. The implicit solvent models with two relaxation time scales are in qualitative agreement with the analytical theories but quantitatively overestimate the rate constants compared to these theories. Analysis of these simulations elucidates the importance of multiple relaxation time scales and the inertial component of the solvent response, as well as potential shortcomings of the analytical theories based on single time scale solvent relaxation models. This implicit solvent approach will enable the simulation of a wide range of ET reactions via the stochastic dynamics of a single collective solvent coordinate with parameters that are relevant to experimentally accessible

  18. Combining vibrational linear-by-part dynamics and kinetic-based decoupling of the dynamics for multiple elastoplastic smooth impacts

    Energy Technology Data Exchange (ETDEWEB)

    Barjau, Ana, E-mail: ana.barjau@upc.edu; Batlle, Joaquim A., E-mail: agullo.batlle@upc.edu; Font-Llagunes, Josep M., E-mail: josep.m.font@upc.edu [Universitat Politècnica de Catalunya, Department of Mechanical Engineering and Biomedical Engineering Research Centre (Spain)

    2015-11-15

    This article proposes a linear-by-part approach for elastoplastic 3D multiple-point smooth impacts in multibody systems with perfect constraints. The model is an extension of a previous version, restricted to the perfectly elastic case, able to account for the high sensitivity to initial conditions and for redundancy without assuming any particular collision sequence (Barjau et al., Multibody Syst. Dyn. 31:497–517, 2014). Energy losses associated with compression and expansion in percussive analysis is a matter as complex as the physical phenomena involved, at the nanoscale level, for different materials. Simplified models can be developed for specific purposes, which can retain the most relevant trends of internal damping and at the same time be suitable for a particular analytical approach of impact mechanics. In the context of this article, energy dissipation due to material deformation is introduced through a linear-by-part elastoplastic model consisting on two elementary sets of springs and dry-friction dampers. The first set accounts for inelastic behavior (energy loss without permanent indentation), whereas the second one introduces plasticity (that is, permanent indentation). In inelastic and plastic collisions, instantaneous unilateral constraints may appear, thus reducing the number of degrees of freedom (DOF) of the system. The calculation of the corresponding normal contact force at the constrained points is then necessary in order to detect whether the constraint holds or disappears (either because a new compression or an expansion phase starts, or because contact is lost). Different simulated application examples are presented and thoroughly discussed.

  19. Regulating multiple externalities

    DEFF Research Database (Denmark)

    Waldo, Staffan; Jensen, Frank; Nielsen, Max

    2016-01-01

    Open access is a well-known externality problem in fisheries causing excess capacity and overfishing. Due to global warming, externality problems from CO2 emissions have gained increased interest. With two externality problems, a first-best optimum can be achieved by using two regulatory instrume......Open access is a well-known externality problem in fisheries causing excess capacity and overfishing. Due to global warming, externality problems from CO2 emissions have gained increased interest. With two externality problems, a first-best optimum can be achieved by using two regulatory...

  20. Structural and dynamical insights on HLA-DR2 complexes that confer susceptibility to multiple sclerosis in Sardinia: a molecular dynamics simulation study.

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    Full Text Available Sardinia is a major Island in the Mediterranean with a high incidence of multiple sclerosis, a chronic autoimmune inflammatory disease of the central nervous system. Disease susceptibility in Sardinian population has been associated with five alleles of major histocompatibility complex (MHC class II DRB1 gene. We performed 120 ns of molecular dynamics simulation on one predisposing and one protective alleles, unbound and in complex with the two relevant peptides: Myelin Basic Protein and Epstein Barr Virus derived peptide. In particular we focused on the MHC peptide binding groove dynamics. The predisposing allele was found to form a stable complex with both the peptides, while the protective allele displayed stability only when bound with myelin peptide. The local flexibility of the MHC was probed dividing the binding groove into four compartments covering the well known peptide anchoring pockets. The predisposing allele in the first half cleft exhibits a narrower and more rigid groove conformation in the presence of myelin peptide. The protective allele shows a similar behavior, while in the second half cleft it displays a narrower and more flexible groove conformation in the presence of viral peptide. We further characterized these dynamical differences by evaluating H-bonds, hydrophobic and stacking interaction networks, finding striking similarities with super-type patterns emerging in other autoimmune diseases. The protective allele shows a defined preferential binding to myelin peptide, as confirmed by binding free energy calculations. All together, we believe the presented molecular analysis could help to design experimental assays, supports the molecular mimicry hypothesis and suggests that propensity to multiple sclerosis in Sardinia could be partly linked to distinct peptide-MHC interaction and binding characteristics of the antigen presentation mechanism.

  1. Dynamic conformational change regulates the protein-DNA recognition: an investigation on binding of a Y-family polymerase to its target DNA.

    Directory of Open Access Journals (Sweden)

    Xiakun Chu

    2014-09-01

    Full Text Available Protein-DNA recognition is a central biological process that governs the life of cells. A protein will often undergo a conformational transition to form the functional complex with its target DNA. The protein conformational dynamics are expected to contribute to the stability and specificity of DNA recognition and therefore may control the functional activity of the protein-DNA complex. Understanding how the conformational dynamics influences the protein-DNA recognition is still challenging. Here, we developed a two-basin structure-based model to explore functional dynamics in Sulfolobus solfataricus DNA Y-family polymerase IV (DPO4 during its binding to DNA. With explicit consideration of non-specific and specific interactions between DPO4 and DNA, we found that DPO4-DNA recognition is comprised of first 3D diffusion, then a short-range adjustment sliding on DNA and finally specific binding. Interestingly, we found that DPO4 is under a conformational equilibrium between multiple states during the binding process and the distributions of the conformations vary at different binding stages. By modulating the strength of the electrostatic interactions, the flexibility of the linker, and the conformational dynamics in DPO4, we drew a clear picture on how DPO4 dynamically regulates the DNA recognition. We argue that the unique features of flexibility and conformational dynamics in DPO4-DNA recognition have direct implications for low-fidelity translesion DNA synthesis, most of which is found to be accomplished by the Y-family DNA polymerases. Our results help complete the description of the DNA synthesis process for the Y-family polymerases. Furthermore, the methods developed here can be widely applied for future investigations on how various proteins recognize and bind specific DNA substrates.

  2. Spatio-temporal dynamics of regulating ecosystem services in Europe – The role of past and future land use change

    NARCIS (Netherlands)

    Sturck, J.; Schulp, C.J.E.; Verburg, P.H.

    2015-01-01

    Land use is a main driver for changes in supply and demand of regulating ecosystem services (ES). Most current ES inventories are static and do not address dynamics of ES supply resulting from historic and future land use change. This paper analyzes the role of land use change for the supply of two

  3. Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Archna P Gupta

    2013-02-01

    Full Text Available Epigenetic mechanisms are emerging as one of the major factors of the dynamics of gene expression in the human malaria parasite, Plasmodium falciparum. To elucidate the role of chromatin remodeling in transcriptional regulation associated with the progression of the P. falciparum intraerythrocytic development cycle (IDC, we mapped the temporal pattern of chromosomal association with histone H3 and H4 modifications using ChIP-on-chip. Here, we have generated a broad integrative epigenomic map of twelve histone modifications during the P. falciparum IDC including H4K5ac, H4K8ac, H4K12ac, H4K16ac, H3K9ac, H3K14ac, H3K56ac, H4K20me1, H4K20me3, H3K4me3, H3K79me3 and H4R3me2. While some modifications were found to be associated with the vast majority of the genome and their occupancy was constant, others showed more specific and highly dynamic distribution. Importantly, eight modifications displaying tight correlations with transcript levels showed differential affinity to distinct genomic regions with H4K8ac occupying predominantly promoter regions while others occurred at the 5' ends of coding sequences. The promoter occupancy of H4K8ac remained unchanged when ectopically inserted at a different locus, indicating the presence of specific DNA elements that recruit histone modifying enzymes regardless of their broad chromatin environment. In addition, we showed the presence of multivalent domains on the genome carrying more than one histone mark, highlighting the importance of combinatorial effects on transcription. Overall, our work portrays a substantial association between chromosomal locations of various epigenetic markers, transcriptional activity and global stage-specific transitions in the epigenome.

  4. Dynamic epigenetic regulation of gene expression during the life cycle of malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Gupta, Archna P; Chin, Wai Hoe; Zhu, Lei; Mok, Sachel; Luah, Yen-Hoon; Lim, Eng-How; Bozdech, Zbynek

    2013-02-01

    Epigenetic mechanisms are emerging as one of the major factors of the dynamics of gene expression in the human malaria parasite, Plasmodium falciparum. To elucidate the role of chromatin remodeling in transcriptional regulation associated with the progression of the P. falciparum intraerythrocytic development cycle (IDC), we mapped the temporal pattern of chromosomal association with histone H3 and H4 modifications using ChIP-on-chip. Here, we have generated a broad integrative epigenomic map of twelve histone modifications during the P. falciparum IDC including H4K5ac, H4K8ac, H4K12ac, H4K16ac, H3K9ac, H3K14ac, H3K56ac, H4K20me1, H4K20me3, H3K4me3, H3K79me3 and H4R3me2. While some modifications were found to be associated with the vast majority of the genome and their occupancy was constant, others showed more specific and highly dynamic distribution. Importantly, eight modifications displaying tight correlations with transcript levels showed differential affinity to distinct genomic regions with H4K8ac occupying predominantly promoter regions while others occurred at the 5' ends of coding sequences. The promoter occupancy of H4K8ac remained unchanged when ectopically inserted at a different locus, indicating the presence of specific DNA elements that recruit histone modifying enzymes regardless of their broad chromatin environment. In addition, we showed the presence of multivalent domains on the genome carrying more than one histone mark, highlighting the importance of combinatorial effects on transcription. Overall, our work portrays a substantial association between chromosomal locations of various epigenetic markers, transcriptional activity and global stage-specific transitions in the epigenome.

  5. KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.

    Directory of Open Access Journals (Sweden)

    Lee B Smith

    Full Text Available Spermatogenesis is a complex process reliant upon interactions between germ cells (GC and supporting somatic cells. Testicular Sertoli cells (SC support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1. We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC from 15.5 days post-coitum (dpc and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives.

  6. Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala.

    Science.gov (United States)

    Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

    2016-02-01

    Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression.

  7. Exploring transcriptional signalling mediated by OsWRKY13, a potential regulator of multiple physiological processes in rice

    Directory of Open Access Journals (Sweden)

    Li Xianghua

    2009-06-01

    Full Text Available Abstract Background Rice transcription regulator OsWRKY13 influences the functioning of more than 500 genes in multiple signalling pathways, with roles in disease resistance, redox homeostasis, abiotic stress responses, and development. Results To determine the putative transcriptional regulation mechanism of OsWRKY13, the putative cis-acting elements of OsWRKY13-influenced genes were analyzed using the whole genome expression profiling of OsWRKY13-activated plants generated with the Affymetrix GeneChip Rice Genome Array. At least 39 transcription factor genes were influenced by OsWRKY13, and 30 of them were downregulated. The promoters of OsWRKY13-upregulated genes were overrepresented with W-boxes for WRKY protein binding, whereas the promoters of OsWRKY13-downregulated genes were enriched with cis-elements putatively for binding of MYB and AP2/EREBP types of transcription factors. Consistent with the distinctive distribution of these cis-elements in up- and downregulated genes, nine WRKY genes were influenced by OsWRKY13 and the promoters of five of them were bound by OsWRKY13 in vitro; all seven differentially expressed AP2/EREBP genes and six of the seven differentially expressed MYB genes were suppressed by in OsWRKY13-activated plants. A subset of OsWRKY13-influenced WRKY genes were involved in host-pathogen interactions. Conclusion These results suggest that OsWRKY13-mediated signalling pathways are partitioned by different transcription factors. WRKY proteins may play important roles in the monitoring of OsWRKY13-upregulated genes and genes involved in pathogen-induced defence responses, whereas MYB and AP2/EREBP proteins may contribute most to the control of OsWRKY13-downregulated genes.

  8. Multiple length peptide-pheromone variants produced by Streptococcus pyogenes directly bind Rgg proteins to confer transcriptional regulation.

    Science.gov (United States)

    Aggarwal, Chaitanya; Jimenez, Juan Cristobal; Nanavati, Dhaval; Federle, Michael J

    2014-08-08

    Streptococcus pyogenes, a human-restricted pathogen, accounts for substantial mortality related to infections worldwide. Recent studies indicate that streptococci produce and respond to several secreted peptide signaling molecules (pheromones), including those known as short hydrophobic peptides (SHPs), to regulate gene expression by a quorum-sensing mechanism. Upon transport into the bacterial cell, pheromones bind to and modulate activity of receptor proteins belonging to the Rgg family of transcription factors. Previously, we reported biofilm regulation by the Rgg2/3 quorum-sensing circuit in S. pyogenes. The aim of this study was to identify the composition of mature pheromones from cell-free culture supernatants that facilitate biofilm formation. Bioluminescent reporters were employed to detect active pheromones in culture supernatants fractionated by reverse-phase chromatography, and mass spectrometry was used to characterize their properties. Surprisingly, multiple SHPs that varied by length were detected. Synthetic peptides of each variant were tested individually using bioluminescence reporters and biofilm growth assays, and although activities differed widely among the group, peptides comprising the C-terminal eight amino acids of the full-length native peptide were most active. Direct Rgg/SHP interactions were determined using a fluorescence polarization assay that utilized FITC-labeled peptide ligands. Peptide receptor affinities were seen to be as low as 500 nm and their binding affinities directly correlated with observed bioactivity. Revelation of naturally produced pheromones along with determination of their affinity for cognate receptors are important steps forward in designing compounds whose purpose is positioned for future therapeutics aimed at treating infections through the interference of bacterial communication. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Dynamic Optimization for IPS2 Resource Allocation Based on Improved Fuzzy Multiple Linear Regression

    Directory of Open Access Journals (Sweden)

    Maokuan Zheng

    2017-01-01

    Full Text Available The study mainly focuses on resource allocation optimization for industrial product-service systems (IPS2. The development of IPS2 leads to sustainable economy by introducing cooperative mechanisms apart from commodity transaction. The randomness and fluctuation of service requests from customers lead to the volatility of IPS2 resource utilization ratio. Three basic rules for resource allocation optimization are put forward to improve system operation efficiency and cut unnecessary costs. An approach based on fuzzy multiple linear regression (FMLR is developed, which integrates the strength and concision of multiple linear regression in data fitting and factor analysis and the merit of fuzzy theory in dealing with uncertain or vague problems, which helps reduce those costs caused by unnecessary resource transfer. The iteration mechanism is introduced in the FMLR algorithm to improve forecasting accuracy. A case study of human resource allocation optimization in construction machinery industry is implemented to test and verify the proposed model.

  10. A multiplicative reinforcement learning model capturing learning dynamics and interindividual variability in mice

    OpenAIRE

    Bathellier, Brice; Tee, Sui Poh; Hrovat, Christina; Rumpel, Simon

    2013-01-01

    Learning speed can strongly differ across individuals. This is seen in humans and animals. Here, we measured learning speed in mice performing a discrimination task and developed a theoretical model based on the reinforcement learning framework to account for differences between individual mice. We found that, when using a multiplicative learning rule, the starting connectivity values of the model strongly determine the shape of learning curves. This is in contrast to current learning models ...

  11. Robust image registration for multiple exposure high dynamic range image synthesis

    Science.gov (United States)

    Yao, Susu

    2011-03-01

    Image registration is an important preprocessing technique in high dynamic range (HDR) image synthesis. This paper proposed a robust image registration method for aligning a group of low dynamic range images (LDR) that are captured with different exposure times. Illumination change and photometric distortion between two images would result in inaccurate registration. We propose to transform intensity image data into phase congruency to eliminate the effect of the changes in image brightness and use phase cross correlation in the Fourier transform domain to perform image registration. Considering the presence of non-overlapped regions due to photometric distortion, evolutionary programming is applied to search for the accurate translation parameters so that the accuracy of registration is able to be achieved at a hundredth of a pixel level. The proposed algorithm works well for under and over-exposed image registration. It has been applied to align LDR images for synthesizing high quality HDR images..

  12. The structure and dynamics of tandem WW domains in a negative regulator of notch signaling, Suppressor of deltex.

    Science.gov (United States)

    Fedoroff, Oleg Y; Townson, Sharon A; Golovanov, Alexander P; Baron, Martin; Avis, Johanna M

    2004-08-13

    WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet, poorly characterized. An important question is whether functional diversity of different WW domain proteins is reflected in the structural organization and ligand interaction mechanisms of their multiple domains. We have determined the solution structure and dynamics of a pair of WW domains (WW3-4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling. We find that the binding of a type 1 PPPY ligand to WW3 stabilizes the structure with effects propagating to the WW4 domain, a domain that is not active for ligand binding. Both WW domains adopt the characteristic triple-stranded beta-sheet structure, and significantly, this is the first example of a WW domain structure to include a domain (WW4) lacking the second conserved Trp (replaced by Phe). The domains are connected by a flexible linker, which allows a hinge-like motion of domains that may be important for the recognition of functionally relevant targets. Our results contrast markedly with those of the only previously determined three-dimensional structure of tandem WW domains, that of the rigidly oriented WW domain pair from the RNA-splicing factor Prp40. Our data illustrate that arrays of WW domains can exhibit a variety of higher order structures and ligand interaction mechanisms.

  13. Neocortical Dynamics at Multiple Scales: EEG Standing Waves, Statistical Mechanics, and Physical Analogs

    OpenAIRE

    Ingber, Lester; Nunez, Paul L.

    2010-01-01

    The dynamic behavior of scalp potentials (EEG) is apparently due to some combination of global and local processes with important top-down and bottom-up interactions across spatial scales. In treating global mechanisms, we stress the importance of myelinated axon propagation delays and periodic boundary conditions in the cortical-white matter system, which is topologically close to a spherical shell. By contrast, the proposed local mechanisms are multiscale interactions between cortical colum...

  14. An index-based framework for assessing patterns and trends in river fragmentation and flow regulation by global dams at multiple scales

    International Nuclear Information System (INIS)

    Grill, Günther; Lehner, Bernhard; Lumsdon, Alexander E; Zarfl, Christiane; MacDonald, Graham K; Reidy Liermann, Catherine

    2015-01-01

    The global number of dam constructions has increased dramatically over the past six decades and is forecast to continue to rise, particularly in less industrialized regions. Identifying development pathways that can deliver the benefits of new infrastructure while also maintaining healthy and productive river systems is a great challenge that requires understanding the multifaceted impacts of dams at a range of scales. New approaches and advanced methodologies are needed to improve predictions of how future dam construction will affect biodiversity, ecosystem functioning, and fluvial geomorphology worldwide, helping to frame a global strategy to achieve sustainable dam development. Here, we respond to this need by applying a graph-based river routing model to simultaneously assess flow regulation and fragmentation by dams at multiple scales using data at high spatial resolution. We calculated the cumulative impact of a set of 6374 large existing dams and 3377 planned or proposed dams on river connectivity and river flow at basin and subbasin scales by fusing two novel indicators to create a holistic dam impact matrix for the period 1930–2030. Static network descriptors such as basin area or channel length are of limited use in hierarchically nested and dynamic river systems, so we developed the river fragmentation index and the river regulation index, which are based on river volume. These indicators are less sensitive to the effects of network configuration, offering increased comparability among studies with disparate hydrographies as well as across scales. Our results indicate that, on a global basis, 48% of river volume is moderately to severely impacted by either flow regulation, fragmentation, or both. Assuming completion of all dams planned and under construction in our future scenario, this number would nearly double to 93%, largely due to major dam construction in the Amazon Basin. We provide evidence for the importance of considering small to medium

  15. [Dynamic hierarchy of regulatory peptides. Structure of the induction relations of regulators as the target for therapeutic agents].

    Science.gov (United States)

    Koroleva, S V; Miasoedov, N F

    2012-01-01

    Based on the database information (literature period 1970-2010 gg.) on the effects of regulatory peptides (RP) and non-peptide neurotransmitters (dopamine, serotonin, norepi-nephrine, acetylcholine) it was analyzed of possible cascade processes of endogenous regulators. It was found that the entire continuum of RP and mediators is a chaotic soup of the ordered three-level compartments. Such a dynamic functional hierarchy of endogenous regulators allows to create start-up and corrective tasks for a variety of physiological functions. Some examples of static and dynamic patterns of induction processes of RP and mediators (that regulate the states of anxiety, depression, learning and memory, feeding behavior, reproductive processes, etc.) are considered.

  16. Soil Gas Dynamics and Microbial Activity in the Unsaturated Zone of a Regulated River

    Science.gov (United States)

    Christensen, H.; Ferencz, S. B.; Cardenas, M. B.; Neilson, B. T.; Bennett, P. C.

    2017-12-01

    Over 60% of the world's rivers are dammed, and are therefore regulated. In some river systems, river regulation is the dominant factor governing fluid exchange and soil gas dynamics in the hyporheic region and overlying unsaturated zone of the river banks. Where this is the case, it is important to understand the effects that an artificially-induced change in river stage can have on the chemical, plant, and microbial components of the unsaturated zone. Daily releases from an upstream dam cause rapid stage fluctuations in the Lower Colorado River east of Austin, Texas. For this study, we utilized an array of water and gas wells along a transect perpendicular to the river to investigate the biogeochemical process occurring in this mixing zone. The gas wells were installed at several depths up to 1.5 meters, and facilitated the continuous monitoring of soil gases as the pulse percolated through the river bank. Water samples collected from the screened wells penetrated to depths below the water table and were analyzed for nutrients, carbon, and major ions. Additionally, two soil cores were taken at different distances from the river and analyzed for soil moisture and grain size. These cores were also analyzed for microbial activity using the total heterotroph count method and the acetylene inhibition technique, a sensitive method of measuring denitrifying activity. The results provide a detailed picture of soil gas flux and biogeochemical processes in the bank environment in a regulated river. Findings indicate that a river pulse that causes a meter-scale change in river stage causes small, centimeter-scale pulses in the water table. We propose that these conditions create an area of elevated microbial respiration at the base of the unsaturated zone that appears to be decoupled from normal diurnal fluctuations. Along the transect, CO2 concentrations increased with increasing depth down to the water table. CO2 concentrations were highest in the time following a pulse

  17. The Effect of Dynamic and Interactive Mathematics Learning Environments (DIMLE), Supporting Multiple Representations, on Perceptions of Elementary Mathematics Pre-Service Teachers in Problem Solving Process

    Science.gov (United States)

    Ozdemir, S.; Reis, Z. Ayvaz

    2013-01-01

    Mathematics is an important discipline, providing crucial tools, such as problem solving, to improve our cognitive abilities. In order to solve a problem, it is better to envision and represent through multiple means. Multiple representations can help a person to redefine a problem with his/her own words in that envisioning process. Dynamic and…

  18. Transforming growth factor alpha (TGFα regulates granulosa cell tumor (GCT cell proliferation and migration through activation of multiple pathways.

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    Full Text Available Granulosa cell tumors (GCTs are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular model. Immunohistochemistry, Western blot and RT-PCR results showed that the ErbB family of receptors is expressed in human GCT tissues and GCT cell lines. RT-PCR results also indicated that TGFα and EGF are expressed in the human granulosa cells and the GCT cell lines, suggesting that TGFα might regulate GCT cell function in an autocrine/paracrine manner. TGFα stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle progression, and cell migration. TGFα rapidly activated EGFR/PI3K/Akt and mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR, P70S6K and S6 proteins following TGFα treatment. TGFα also rapidly activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFα treatment. Whereas TGFα triggered a transient activation of Akt, it induced a sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells with TGFα resulted in a significant increase in cyclin D2 and a decrease in p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa cell tumorigenesis. In conclusion, TGFα, via multiple signaling pathways, regulates KGN cell proliferation and migration and may play an important role in the growth and metastasis of GCTs.

  19. A Dynamic Control Strategy for Hybrid Electric Vehicles Based on Parameter Optimization for Multiple Driving Cycles and Driving Pattern Recognition

    Directory of Open Access Journals (Sweden)

    Zhenzhen Lei

    2017-01-01

    Full Text Available The driving pattern has an important influence on the parameter optimization of the energy management strategy (EMS for hybrid electric vehicles (HEVs. A new algorithm using simulated annealing particle swarm optimization (SA-PSO is proposed for parameter optimization of both the power system and control strategy of HEVs based on multiple driving cycles in order to realize the minimum fuel consumption without impairing the dynamic performance. Furthermore, taking the unknown of the actual driving cycle into consideration, an optimization method of the dynamic EMS based on driving pattern recognition is proposed in this paper. The simulation verifications for the optimized EMS based on multiple driving cycles and driving pattern recognition are carried out using Matlab/Simulink platform. The results show that compared with the original EMS, the former strategy reduces the fuel consumption by 4.36% and the latter one reduces the fuel consumption by 11.68%. A road test on the prototype vehicle is conducted and the effectiveness of the proposed EMS is validated by the test data.

  20. Liquid chromatography-electrospray ionization tandem mass spectrometry and dynamic multiple reaction monitoring method for determining multiple pesticide residues in tomato.

    Science.gov (United States)

    Andrade, G C R M; Monteiro, S H; Francisco, J G; Figueiredo, L A; Botelho, R G; Tornisielo, V L

    2015-05-15

    A quick and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method, using dynamic multiple reaction monitoring and a 1.8-μm particle size analytical column, was developed to determine 57 pesticides in tomato in a 13-min run. QuEChERS (quick, easy, cheap, effective, rugged, and safe) method for samples preparations and validations was carried out in compliance with EU SANCO guidelines. The method was applied to 58 tomato samples. More than 84% of the compounds investigated showed limits of detection equal to or lower than 5 mg kg(-1). A mild (50%) matrix effect was observed for 72%, 25%, and 3% of the pesticides studied, respectively. Eighty-one percent of the pesticides showed recoveries ranging between 70% and 120%. Twelve pesticides were detected in 35 samples, all below the maximum residue levels permitted in the Brazilian legislation; 15 samples exceeded the maximum residue levels established by the EU legislation for methamidophos; and 10 exceeded limits for acephate and four for bromuconazole. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds.

    Science.gov (United States)

    Jaganathan, Ganesh K; Han, Yingying; Li, Weijie; Song, Danping; Song, Xiaoyan; Shen, Mengqi; Zhou, Qiang; Zhang, Chenxue; Liu, Baolin

    2017-03-13

    The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h -1 ) suffered significantly higher membrane damage at temperature between -20 °C and -10 °C than slow cooled (3 °Ch -1 ) seeds (P  0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to -20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes.

  2. Robust Takagi-Sugeno Fuzzy Dynamic Regulator for Trajectory Tracking of a Pendulum-Cart System

    Directory of Open Access Journals (Sweden)

    Miguel A. Llama

    2015-01-01

    Full Text Available Starting from a nonlinear model for a pendulum-cart system, on which viscous friction is considered, a Takagi-Sugeno (T-S fuzzy augmented model (TSFAM as well as a TSFAM with uncertainty (TSFAMwU is proposed. Since the design of a T-S fuzzy controller is based on the T-S fuzzy model of the nonlinear system, then, to address the trajectory tracking problem of the pendulum-cart system, three T-S fuzzy controllers are proposed via parallel distributed compensation: (1 a T-S fuzzy servo controller (TSFSC designed from the TSFAM; (2 a robust TSFSC (RTSFSC designed from the TSFAMwU; and (3 a robust T-S fuzzy dynamic regulator (RTSFDR designed from the RTSFSC with the addition of a T-S fuzzy observer, which estimates cart and pendulum velocities. Both TSFAM and TSFAMwU are comprised of two fuzzy rules and designed via local approximation in fuzzy partition spaces technique. Feedback gains for the three fuzzy controllers are obtained via linear matrix inequalities approach. A swing-up controller is developed to swing the pendulum up from its pendant position to its upright position. Real-time experiments validate the effectiveness of the proposed schemes, keeping the pendulum in its upright position while the cart follows a reference signal, standing out the RTSFDR.

  3. Adaptive dynamic programming for discrete-time linear quadratic regulation based on multirate generalised policy iteration

    Science.gov (United States)

    Chun, Tae Yoon; Lee, Jae Young; Park, Jin Bae; Choi, Yoon Ho

    2018-06-01

    In this paper, we propose two multirate generalised policy iteration (GPI) algorithms applied to discrete-time linear quadratic regulation problems. The proposed algorithms are extensions of the existing GPI algorithm that consists of the approximate policy evaluation and policy improvement steps. The two proposed schemes, named heuristic dynamic programming (HDP) and dual HDP (DHP), based on multirate GPI, use multi-step estimation (M-step Bellman equation) at the approximate policy evaluation step for estimating the value function and its gradient called costate, respectively. Then, we show that these two methods with the same update horizon can be considered equivalent in the iteration domain. Furthermore, monotonically increasing and decreasing convergences, so called value iteration (VI)-mode and policy iteration (PI)-mode convergences, are proved to hold for the proposed multirate GPIs. Further, general convergence properties in terms of eigenvalues are also studied. The data-driven online implementation methods for the proposed HDP and DHP are demonstrated and finally, we present the results of numerical simulations performed to verify the effectiveness of the proposed methods.

  4. Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factors.

    Science.gov (United States)

    Moriel-Carretero, María; Ovejero, Sara; Gérus-Durand, Marie; Vryzas, Dimos; Constantinou, Angelos

    2017-12-04

    Proteins disabled in the cancer-prone disorder Fanconi anemia (FA) ensure the maintenance of chromosomal stability during DNA replication. FA proteins regulate replication dynamics, coordinate replication-coupled repair of interstrand DNA cross-links, and mitigate conflicts between replication and transcription. Here we show that FANCI and FANCD2 associate with splicing factor 3B1 (SF3B1), a key spliceosomal protein of the U2 small nuclear ribonucleoprotein (U2 snRNP). FANCI is in close proximity to SF3B1 in the nucleoplasm of interphase and mitotic cells. Furthermore, we find that DNA replication stress induces the release of SF3B1 from nuclear speckles in a manner that depends on FANCI and on the activity of the checkpoint kinase ATR. In chromatin, both FANCD2 and FANCI associate with SF3B1, prevent accumulation of postcatalytic intron lariats, and contribute to the timely eviction of splicing factors. We propose that FANCD2 and FANCI contribute to the organization of functional domains in chromatin, ensuring the coordination of DNA replication and cotranscriptional processes. © 2017 Moriel-Carretero et al.

  5. Adaptive temperature regulation in the little bird in winter: predictions from a stochastic dynamic programming model.

    Science.gov (United States)

    Brodin, Anders; Nilsson, Jan-Åke; Nord, Andreas

    2017-09-01

    Several species of small birds are resident in boreal forests where environmental temperatures can be -20 to -30 °C, or even lower, in winter. As winter days are short, and food is scarce, winter survival is a challenge for small endothermic animals. A bird of this size will have to gain almost 10% of its lean body mass in fat every day to sustain overnight metabolism. Birds such as parids (titmice and chickadees) can use facultative hypothermia, a process in which body temperature is actively down-regulated to a specific level, to reduce heat loss and thus save energy. During cold winter nights, these birds may decrease body temperature from the normal from 42 ° down to 35 °C, or even lower in some species. However, birds are unable to move in this deep hypothermic state, making it a risky strategy if predators are around. Why, then, do small northern birds enter a potentially dangerous physiological state for a relatively small reduction in energy expenditure? We used stochastic dynamic programming to investigate this. Our model suggests that the use of nocturnal hypothermia at night is paramount in these biomes, as it would increase winter survival for a small northern bird by 58% over a winter of 100 days. Our model also explains the phenomenon known as winter fattening, and its relationship to thermoregulation, in northern birds.

  6. Angiogenin enhances cell migration by regulating stress fiber assembly and focal adhesion dynamics.

    Directory of Open Access Journals (Sweden)

    Saisai Wei

    Full Text Available Angiogenin (ANG acts on both vascular endothelial cells and cancer cells, but the underlying mechanism remains elusive. In this study, we carried out a co-immunoprecipitation assay in HeLa cells and identified 14 potential ANG-interacting proteins. Among these proteins, β-actin, α-actinin 4, and non-muscle myosin heavy chain 9 are stress fiber components and involved in cytoskeleton organization and movement, which prompted us to investigate the mechanism of action of ANG in cell migration. Upon confirmation of the interactions between ANG and the three proteins, further studies revealed that ANG co-localized with β-actin and α-actinin 4 at the leading edge of migrating cells. Down-regulation of ANG resulted in fewer but thicker stress fibers with less dynamics, which was associated with the enlargements of focal adhesions. The focal adhesion kinase activity and cell migration capacity were significantly decreased in ANG-deficient cells. Taken together, our data demonstrated that the existence of ANG in the cytoplasm optimizes stress fiber assembly and focal adhesion formation to accommodate cell migration. The finding that ANG promoted cancer cell migration might provide new clues for tumor metastasis research.

  7. Dynamic simulation platform to verify the performance of the reactor regulating system for a research reactor

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-07-01

    Digital instrumentation and controls system technique is being introduced in new constructed research reactor or life extension of older research reactor. Digital systems are easy to change and optimize but the validated process for them is required. Also, to reduce project risk or cost, we have to make it sure that configuration and control functions is right before the commissioning phase on research reactor. For this purpose, simulators have been widely used in developing control systems in automotive and aerospace industries. In these literatures, however, very few of these can be found regarding test on the control system of research reactor with simulator. Therefore, this paper proposes a simulation platform to verify the performance of RRS (Reactor Regulating System) for research reactor. This simulation platform consists of the reactor simulation model and the interface module. This simulation platform is applied to I and C upgrade project of TRIGA reactor, and many problems of RRS configuration were found and solved. And it proved that the dynamic performance testing based on simulator enables significant time saving and improves economics and quality for RRS in the system test phase. (authors)

  8. Multiple superdeformed bands in sup 194 Hg and their dynamical moments of inertia

    Energy Technology Data Exchange (ETDEWEB)

    Riley, M.A.; Cullen, D.M.; Alderson, A.; Ali, I.; Fallon, P.; Forsyth, P.D.; Hanna, F.; Mullins, S.M.; Roberts, J.W.; Sharpey-Schafer, J.F.; Twin, P.J. (Liverpool Univ. (UK). Oliver Lodge Lab.); Poynter, R.; Wadsworth, R. (York Univ. (UK). Dept. of Physics); Bentley, M.A.; Bruce, A.M.; Simpson, J. (Science and Engineering Research Council, Daresbury (UK). Daresbury Lab.); Sletten, G. (Niels Bohr Inst., Roskilde (Denmark). Tandem Accelerator Lab.); Nazarewicz, W. (Liverpool Univ. (UK). Oliver Lodge Lab. Politechnika Warszawska (Poland). Inst. Fizyki); Bengtsson, T. (Lund Inst. of Tech. (Sweden). Dept. of Mathematical Physics); Wyss, R. (Manne Siegbahn Inst. of Physics, Stockholm (Sweden))

    1990-05-28

    Three superdeformed bands have been observed in {sup 194}Hg. The dynamical moment of inertia J{sup (2)} of all three bands is observed to increase by 30-40% over the frequency range {Dirac h}{omega}=0.1-0.4 MeV. This phenomena can be understood in terms of the gradual alignment of pairs of high-j intruder orbitals within the framework of the cranked Woods-Saxon and Nilsson models including pairing. The calculations together with the observed J{sup (2)} behaviour of the three bands indicate that pairing correlations in the superdeformed minimum are rather weak. (orig.).

  9. On the limit dynamics of systems with infinite multiple degrees of freedom

    Energy Technology Data Exchange (ETDEWEB)

    Braun, W A

    1977-01-01

    By using N/sup -2/ phi (g sub i - g sub j) regular pair interactions, it is shown that, for n approaching infinity, the Vlasovdynamics is the omega meson resonances -limit of the classical canonical N-particle-dynamics. Propagation of molecular chaos holds in this limit and the fluctuations converge to a Gaussian stochastic process, which is, however, non-Markovian. A model of a nerve membrane is studied in the limit of singular interaction with Fermion reservoirs. The resulting axon equations have the same structure as the Hodgkin Huxley equations. Recently proven theorems are used on nonlinear diffusion equations to show the existance of a propagating pulse solution.

  10. Key Process Uncertainties in Soil Carbon Dynamics: Comparing Multiple Model Structures and Observational Meta-analysis

    Science.gov (United States)

    Sulman, B. N.; Moore, J.; Averill, C.; Abramoff, R. Z.; Bradford, M.; Classen, A. T.; Hartman, M. D.; Kivlin, S. N.; Luo, Y.; Mayes, M. A.; Morrison, E. W.; Riley, W. J.; Salazar, A.; Schimel, J.; Sridhar, B.; Tang, J.; Wang, G.; Wieder, W. R.

    2016-12-01

    Soil carbon (C) dynamics are crucial to understanding and predicting C cycle responses to global change and soil C modeling is a key tool for understanding these dynamics. While first order model structures have historically dominated this area, a recent proliferation of alternative model structures representing different assumptions about microbial activity and mineral protection is providing new opportunities to explore process uncertainties related to soil C dynamics. We conducted idealized simulations of soil C responses to warming and litter addition using models from five research groups that incorporated different sets of assumptions about processes governing soil C decomposition and stabilization. We conducted a meta-analysis of published warming and C addition experiments for comparison with simulations. Assumptions related to mineral protection and microbial dynamics drove strong differences among models. In response to C additions, some models predicted long-term C accumulation while others predicted transient increases that were counteracted by accelerating decomposition. In experimental manipulations, doubling litter addition did not change soil C stocks in studies spanning as long as two decades. This result agreed with simulations from models with strong microbial growth responses and limited mineral sorption capacity. In observations, warming initially drove soil C loss via increased CO2 production, but in some studies soil C rebounded and increased over decadal time scales. In contrast, all models predicted sustained C losses under warming. The disagreement with experimental results could be explained by physiological or community-level acclimation, or by warming-related changes in plant growth. In addition to the role of microbial activity, assumptions related to mineral sorption and protected C played a key role in driving long-term model responses. In general, simulations were similar in their initial responses to perturbations but diverged over

  11. Towards the prediction of multiple necking during dynamic extension of round bar: linear stability approach versus finite element calculations

    International Nuclear Information System (INIS)

    Maï, S El; Petit, J; Mercier, S; Molinari, A

    2014-01-01

    The fragmentation of structures subject to dynamic conditions is a matter of interest for civil industries as well as for Defence institutions. Dynamic expansions of structures, such as cylinders or rings, have been performed to obtain crucial information on fragment distributions. Many authors have proposed to capture by FEA the experimental distribution of fragment size by introducing in the FE model a perturbation. Stability and bifurcation analyses have also been proposed to describe the evolution of the perturbation growth rate. In the proposed contribution, the multiple necking of a round bar in dynamic tensile loading is analysed by the FE method. A perturbation on the initial flow stress is introduced in the numerical model to trigger instabilities. The onset time and the dominant mode of necking have been characterized precisely and showed power law evolutions, with the loading velocities and moderately with the amplitudes and the cell sizes of the perturbations. In the second part of the paper, the development of linear stability analysis and the use of salient criteria in terms of the growth rate of perturbations enabled comparisons with the numerical results. A good correlation in terms of onset time of instabilities and of number of necks is shown.

  12. Neocortical dynamics at multiple scales: EEG standing waves, statistical mechanics, and physical analogs.

    Science.gov (United States)

    Ingber, Lester; Nunez, Paul L

    2011-02-01

    The dynamic behavior of scalp potentials (EEG) is apparently due to some combination of global and local processes with important top-down and bottom-up interactions across spatial scales. In treating global mechanisms, we stress the importance of myelinated axon propagation delays and periodic boundary conditions in the cortical-white matter system, which is topologically close to a spherical shell. By contrast, the proposed local mechanisms are multiscale interactions between cortical columns via short-ranged non-myelinated fibers. A mechanical model consisting of a stretched string with attached nonlinear springs demonstrates the general idea. The string produces standing waves analogous to large-scale coherent EEG observed in some brain states. The attached springs are analogous to the smaller (mesoscopic) scale columnar dynamics. Generally, we expect string displacement and EEG at all scales to result from both global and local phenomena. A statistical mechanics of neocortical interactions (SMNI) calculates oscillatory behavior consistent with typical EEG, within columns, between neighboring columns via short-ranged non-myelinated fibers, across cortical regions via myelinated fibers, and also derives a string equation consistent with the global EEG model. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. On the nonlinear dynamics of trolling-mode AFM: Analytical solution using multiple time scales method

    Science.gov (United States)

    Sajjadi, Mohammadreza; Pishkenari, Hossein Nejat; Vossoughi, Gholamreza

    2018-06-01

    Trolling mode atomic force microscopy (TR-AFM) has resolved many imaging problems by a considerable reduction of the liquid-resonator interaction forces in liquid environments. The present study develops a nonlinear model of the meniscus force exerted to the nanoneedle of TR-AFM and presents an analytical solution to the distributed-parameter model of TR-AFM resonator utilizing multiple time scales (MTS) method. Based on the developed analytical solution, the frequency-response curves of the resonator operation in air and liquid (for different penetration length of the nanoneedle) are obtained. The closed-form analytical solution and the frequency-response curves are validated by the comparison with both the finite element solution of the main partial differential equations and the experimental observations. The effect of excitation angle of the resonator on horizontal oscillation of the probe tip and the effect of different parameters on the frequency-response of the system are investigated.

  14. Dynamic Allocation and Efficient Distribution of Data Among Multiple Clouds Using Network Coding

    DEFF Research Database (Denmark)

    Sipos, Marton A.; Fitzek, Frank; Roetter, Daniel Enrique Lucani

    2014-01-01

    Distributed storage has attracted large interest lately from both industry and researchers as a flexible, cost-efficient, high performance, and potentially secure solution for geographically distributed data centers, edge caching or sharing storage among users. This paper studies the benefits...... of random linear network coding to exploit multiple commercially available cloud storage providers simultaneously with the possibility to constantly adapt to changing cloud performance in order to optimize data retrieval times. The main contribution of this paper is a new data distribution mechanisms...... that cleverly stores and moves data among different clouds in order to optimize performance. Furthermore, we investigate the trade-offs among storage space, reliability and data retrieval speed for our proposed scheme. By means of real-world implementation and measurements using well-known and publicly...

  15. Dynamics of a multiple-pulse-driven x-ray laser plasma

    International Nuclear Information System (INIS)

    Wan, A.S.; Da Silva, L.B.; Moreno, J.C.; Cauble, R.; Celliers, P.; Dalhed, H.E. Jr.; Koch, J.A.; Nilsen, J.

    1996-01-01

    In this paper we describe experimental and computational studies of multiple-pulse-driven laser plasma, which is the gain medium for a neon-like yttrium x-ray laser. Near-field emission profiles have been measured both with and without reinjection of the x-ray laser photons to couple with the amplifying medium created by later pulses using an external multilayer mirror. From the temporal and spatial evolution of the near-field emission profiles we can examine the pulse-to-pulse variation of the x-ray laser plasma due to changes in the hydrodynamics, laser deposition, and the injecting of x-ray laser photons back into an amplifying x-ray laser plasma. Using a combination of radiation hydrodynamics, atomic kinetics, and ray propagation codes, reasonable agreement has been obtained between simulations and the experimental results. copyright 1996 American Institute of Physics

  16. Langevin dynamics for vector variables driven by multiplicative white noise: A functional formalism

    Science.gov (United States)

    Moreno, Miguel Vera; Arenas, Zochil González; Barci, Daniel G.

    2015-04-01

    We discuss general multidimensional stochastic processes driven by a system of Langevin equations with multiplicative white noise. In particular, we address the problem of how time reversal diffusion processes are affected by the variety of conventions available to deal with stochastic integrals. We present a functional formalism to build up the generating functional of correlation functions without any type of discretization of the Langevin equations at any intermediate step. The generating functional is characterized by a functional integration over two sets of commuting variables, as well as Grassmann variables. In this representation, time reversal transformation became a linear transformation in the extended variables, simplifying in this way the complexity introduced by the mixture of prescriptions and the associated calculus rules. The stochastic calculus is codified in our formalism in the structure of the Grassmann algebra. We study some examples such as higher order derivative Langevin equations and the functional representation of the micromagnetic stochastic Landau-Lifshitz-Gilbert equation.

  17. Influence of pollen transport dynamics on sire profiles and multiple paternity in flowering plants.

    Directory of Open Access Journals (Sweden)

    Randall J Mitchell

    Full Text Available In many flowering plants individual fruits contain a mixture of half- and full- siblings, reflecting pollination by several fathers. To better understand the mechanisms generating multiple paternity within fruits we present a theoretical framework linking pollen carryover with patterns of pollinator movement. This 'sire profile' model predicts that species with more extensive pollen carryover will have a greater number of mates. It also predicts that flowers on large displays, which are often probed consecutively during a single pollinator visitation sequence, will have a lower effective number of mates. We compared these predictions with observed values for bumble bee-pollinated Mimulus ringens, which has restricted carryover, and hummingbird-pollinated Ipomopsis aggregata, which has extensive carryover. The model correctly predicted that the effective number of mates is much higher in the species with more extensive carryover. This work extends our knowledge of plant mating systems by highlighting mechanisms influencing the genetic composition of sibships.

  18. Dynamic biometric identification from multiple views using the GLBP-TOP method.

    Science.gov (United States)

    Wang, Yu; Shen, Xuanjing; Chen, Haipeng; Zhai, Yujie

    2014-01-01

    To realize effective and rapid dynamic biometric identification with low computational complexity, a video-based facial texture program that extracts local binary patterns from three orthogonal planes in the frequency domain of the Gabor transform (GLBP-TOP) was proposed. Firstly, each normalized face was transformed by Gabor wavelet to get the enhanced Gabor magnitude map, and then the LBP-TOP operator was applied to the maps to extract video texture. Finally, weighted Chi square statistics based on the Fisher Criterion were used to realize the identification. The proposed algorithm was proved effective through the biometric experiments using the Honda/UCSD database, and was robust against changes of illumination and expressions.

  19. Comparative evolutionary diversity and phylogenetic structure across multiple forest dynamics plots: a mega-phylogeny approach

    Directory of Open Access Journals (Sweden)

    David Lee Erickson

    2014-11-01

    Full Text Available Forest dynamics plots, which now span longitudes, latitudes, and habitat types across the globe, offer unparalleled insights into the ecological and evolutionary processes that determine how species are assembled into communities. Understanding phylogenetic relationships among species in a community has become an important component of assessing assembly processes. However, the application of evolutionary information to questions in community ecology has been limited in large part by the lack of accurate estimates of phylogenetic relationships among individual species found within communities, and is particularly limiting in comparisons between communities. Therefore, streamlining and maximizing the information content of these community phylogenies is a priority. To test the viability and advantage of a multi-community phylogeny, we constructed a multi-plot mega-phylogeny of 1,347 species of trees across 15 forest dynamics plots in the ForestGEO network using DNA barcode sequence data (rbcL, matK and psbA-trnH and compared community phylogenies for each individual plot with respect to support for topology and branch lengths, which affect evolutionary inference of community processes. The levels of taxonomic differentiation across the phylogeny were examined by quantifying the frequency of resolved nodes throughout. In addition, three phylogenetic distance metrics that are commonly used to infer assembly processes were estimated for each plot (Phylogenetic Distance [PD], Mean Phylogenetic Distance [MPD], and Mean Nearest Taxon Distance [MNTD]. Lastly, we examine the partitioning of phylogenetic diversity among community plots through quantification of inter-community MPD and MNTD. Overall, evolutionary relationships were highly resolved across the DNA barcode-based mega-phylogeny, and phylogenetic resolution for each community plot was improved when estimated within the context of the mega-phylogeny. Likewise, when compared with phylogenies for

  20. A kinetic model of trp-cage folding from multiple biased molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Fabrizio Marinelli

    2009-08-01

    Full Text Available Trp-cage is a designed 20-residue polypeptide that, in spite of its size, shares several features with larger globular proteins.Although the system has been intensively investigated experimentally and theoretically, its folding mechanism is not yet fully understood. Indeed, some experiments suggest a two-state behavior, while others point to the presence of intermediates. In this work we show that the results of a bias-exchange metadynamics simulation can be used for constructing a detailed thermodynamic and kinetic model of the system. The model, although constructed from a biased simulation, has a quality similar to those extracted from the analysis of long unbiased molecular dynamics trajectories. This is demonstrated by a careful benchmark of the approach on a smaller system, the solvated Ace-Ala3-Nme peptide. For theTrp-cage folding, the model predicts that the relaxation time of 3100 ns observed experimentally is due to the presence of a compact molten globule-like conformation. This state has an occupancy of only 3% at 300 K, but acts as a kinetic trap.Instead, non-compact structures relax to the folded state on the sub-microsecond timescale. The model also predicts the presence of a state at Calpha-RMSD of 4.4 A from the NMR structure in which the Trp strongly interacts with Pro12. This state can explain the abnormal temperature dependence of the Pro12-delta3 and Gly11-alpha3 chemical shifts. The structures of the two most stable misfolded intermediates are in agreement with NMR experiments on the unfolded protein. Our work shows that, using biased molecular dynamics trajectories, it is possible to construct a model describing in detail the Trp-cage folding kinetics and thermodynamics in agreement with experimental data.

  1. Dynamic autophagic activity affected the development of thoracic aortic dissection by regulating functional properties of smooth muscle cells

    International Nuclear Information System (INIS)

    Wang, Yang; Zhao, Zhi-Min; Zhang, Guan-Xin; Yang, Fan; Yan, Yan; Liu, Su-Xuan; Li, Song-Hua; Wang, Guo-Kun; Xu, Zhi-Yun

    2016-01-01

    The aortic medial degeneration is the key histopathologic feature of Thoracic aortic dissection (TAD). The aim of this study was to identify the change of autophagic activity in the aortic wall during TAD development, and to explore the roles of autophagy on regulating functional properties of smooth muscle cells (SMCs). Firstly, compared with control group (n = 11), the increased expression of autophagic markers Beclin1 and LC3 was detected in the aortic wall from TAD group (n = 23) by immunochemistry and western blot. We found that more autophagic vacuoles were present in the aortic wall of TAD patients using Transmission electron microscopy. Next, autophagic activity was examined in AD mice model established by β-aminopropionitrile fumarate (BAPN) and angiotensin II. Immunochemistry proved that autophagic activity was dynamically changed during AD development. Beclin1 and LC3 were detected up-regulated in the aortic wall in the second week after BAPN feeding, earlier than the fragmentation or loss of elastic fibers. When AD occurred in the 4th week, the expression of Beclin1 and LC3 began to decrease, but still higher than the control. Furthermore, autophagy was found to inhibit starvation-induced apoptosis of SMCs. Meanwhile, blockage of autophagy could suppress PDGF-induced phenotypic switch of SMCs. Taken together, autophagic activity was dynamically changed in the aortic wall during TAD development. The abnormal autophagy could regulate the functional properties of aortic SMCs, which might be the potential pathogenesis of TAD. - Highlights: • Autophagy is up-regulated in aorta wall from thoracic aorta dissection (TAD) patient. • Autophagic activity is dynamically changed during TAD development. • Dynamically change of autophagy is associated with pathological process of TAD. • Autophagy participate in the development of TAD by regulating function of SMCs.

  2. Quantitative transcription dynamic analysis reveals candidate genes and key regulators for ethanol tolerance in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Ma Menggen

    2010-06-01

    Full Text Available Abstract Background Derived from our lignocellulosic conversion inhibitor-tolerant yeast, we generated an ethanol-tolerant strain Saccharomyces cerevisiae NRRL Y-50316 by enforced evolutionary adaptation. Using a newly developed robust mRNA reference and a master equation unifying gene expression data analyses, we investigated comparative quantitative transcription dynamics of 175 genes selected from previous studies for an ethanol-tolerant yeast and its closely related parental strain. Results A highly fitted master equation was established and applied for quantitative gene expression analyses using pathway-based qRT-PCR array assays. The ethanol-tolerant Y-50316 displayed significantly enriched background of mRNA abundance for at least 35 genes without ethanol challenge compared with its parental strain Y-50049. Under the ethanol challenge, the tolerant Y-50316 responded in consistent expressions over time for numerous genes belonging to groups of heat shock proteins, trehalose metabolism, glycolysis, pentose phosphate pathway, fatty acid metabolism, amino acid biosynthesis, pleiotropic drug resistance gene family and transcription factors. The parental strain showed repressed expressions for many genes and was unable to withstand the ethanol stress and establish a viable culture and fermentation. The distinct expression dynamics between the two strains and their close association with cell growth, viability and ethanol fermentation profiles distinguished the tolerance-response from the stress-response in yeast under the ethanol challenge. At least 82 genes were identified as candidate and key genes for ethanol-tolerance and subsequent fermentation under the stress. Among which, 36 genes were newly recognized by the present study. Most of the ethanol-tolerance candidate genes were found to share protein binding motifs of transcription factors Msn4p/Msn2p, Yap1p, Hsf1p and Pdr1p/Pdr3p. Conclusion Enriched background of transcription abundance

  3. The Effects of Multiple-Joint Isokinetic Resistance Training on Maximal Isokinetic and Dynamic Muscle Strength and Local Muscular Endurance

    Directory of Open Access Journals (Sweden)

    Nicholas A. Ratamess, Noah A. Beller, Adam M. Gonzalez, Gregory E. Spatz, Jay R. Hoffman, Ryan E. Ross, Avery D. Faigenbaum, Jie Kang

    2016-03-01

    Full Text Available The transfer of training effects of multiple-joint isokinetic resistance training to dynamic exercise performance remain poorly understood. Thus, the purpose of the present study was to investigate the magnitude of isokinetic and dynamic one repetition-maximum (1RM strength and local muscular endurance increases after 6 weeks of multiple-joint isokinetic resistance training. Seventeen women were randomly assigned to either an isokinetic resistance training group (IRT or a non-exercising control group (CTL. The IRT group underwent 6 weeks of training (2 days per week consisting of 5 sets of 6-10 repetitions at 75-85% of subjects’ peak strength for the isokinetic chest press and seated row exercises at an average linear velocity of 0.15 m s-1 [3-sec concentric (CON and 3-sec eccentric (ECC phases]. Peak CON and ECC force during the chest press and row, 1RM bench press and bent-over row, and maximum number of modified push-ups were assessed pre and post training. A 2 x 2 analysis of variance with repeated measures and Tukey’s post hoc tests were used for data analysis. The results showed that 1RM bench press (from 38.6 ± 6.7 to 43.0 ± 5.9 kg, 1RM bent-over row (from 40.4 ± 7.7 to 45.5 ± 7.5 kg, and the maximal number of modified push-ups (from 39.5 ± 13.6 to 55.3 ± 13.1 repetitions increased significantly only in the IRT group. Peak isokinetic CON and ECC force in the chest press and row significantly increased in the IRT group. No differences were shown in the CTL group for any measure. These data indicate 6 weeks of multiple-joint isokinetic resistance training increases dynamic muscle strength and local muscular endurance performance in addition to specific isokinetic strength gains in women.

  4. Profiles of self-concept, goal orientation, and self-regulation in students with physical, intellectual, and multiple disabilities: Implications for instructional support.

    Science.gov (United States)

    Varsamis, Panagiotis; Agaliotis, Ioannis

    2011-01-01

    The present study explored physical self-concept, goal orientation in sport, and self-regulation in regard to a motor task, in 75 secondary students with physical, intellectual, and multiple disabilities, who were educated in the same special education units. It was found that students with intellectual disabilities generally presented a positive profile in all three psychosocial constructs, whereas students with physical disabilities presented low scores in most measures. Students with multiple disabilities did not differ essentially from students with intellectual disability in regard to physical self-concept and goal orientation; however, they compared unfavorably to them regarding self-regulation. The delineation of a distinct and defendable profile of self-concept, goal orientation, and self-regulation for each disability group allows the formulation of proposals for the implementation of appropriate instructional programs for students belonging to the above mentioned categories. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Dynamic regulation of mechanosensitive channels: capacitance used to monitor patch tension in real time

    Science.gov (United States)

    Suchyna, Thomas M.; Besch, Steven R.; Sachs, Frederick

    2004-03-01

    All cells, from bacteria to human, are mechanically sensitive. The most rapid of these membrane protein transducers are mechanosensitive ion channels, ionic pores in the membrane that open and close in response to membrane tension. In specific sensory organs, these channels serve the senses of touch and hearing, and inform the central nervous system about the filling of hollow organs such as the bladder. Non-specialized cells use these channels to report on changes in cell volume and local strain. To preserve dynamic sensitivity, sensory receptors adapt to steady-state stimuli. Here we show that in rat astrocytes, the most abundant cells in the brain, this apparent adaptation to the stimulus is actually an inactivation. We have been able to track the time course of local strain by measuring attofarad changes in membrane capacitance and show that it is not correlated with loss of channel activity. The reduction in current with time is caused by an increased occupancy of low conductance states, and a reduction in the probability of opening, not a relaxation of local stress. The occupancy of these substates depends on the integrity of the cell's cytoplasm. However, while disruption of the cytoskeleton leads to a loss of inactivation, it leaves activation unaffected. The activation process is voltage-insensitive, closely correlated with changes in capacitance, and seems to arise solely from stress in the bilayer. The inactivation rate decreases with depolarization, and kinetic analysis suggests that the process involves multiple cytoplasmic ligands. Surprisingly, multivalent ions such as Gd+3 and Ca+2 that bind to the lipids and affect channel gating, do not affect the strain-induced increase in membrane capacitance; contrary to expectations, membrane elasticity is unchanged.

  6. Quantitative tissue-specific dynamics of in vivo GILZ mRNA expression and regulation by endogenous and exogenous glucocorticoids.

    Science.gov (United States)

    Ayyar, Vivaswath S; Almon, Richard R; Jusko, William J; DuBois, Debra C

    2015-06-01

    Glucocorticoids (GC) are steroid hormones, which regulate metabolism and immune function. Synthetic GCs, or corticosteroids (CS), have appreciable clinical utility via their ability to suppress inflammation in immune-mediated diseases like asthma and rheumatoid arthritis. Recent work has provided insight to novel GC-induced genes that mediate their anti-inflammatory effects, including glucocorticoid-induced leucine zipper (GILZ). Since GILZ comprises an important part of GC action, its regulation by both drug and hormone will influence CS therapy. In addition, GILZ expression is often employed as a biomarker of GC action, which requires judicious selection of sampling time. Understanding the in vivo regulation of GILZ mRNA expression over time will provide insight into both the physiological regulation of GILZ by endogenous GC and the dynamics of its enhancement by CS. A highly quantitative qRT-PCR assay was developed for measuring GILZ mRNA expression in tissues obtained from normal and CS-treated rats. This assay was applied to measure GILZ mRNA expression in eight tissues; to determine its endogenous regulation over time; and to characterize its dynamics in adipose tissue, muscle, and liver following treatment with CS. We demonstrate that GILZ mRNA is expressed in several tissues. GILZ mRNA expression in adipose tissue displayed a robust circadian rhythm that was entrained with the circadian oscillation of endogenous corticosterone; and is strongly enhanced by acute and chronic dosing. Single dosing also enhanced GILZ mRNA in muscle and liver, but the dynamics varied. In conclusion, GILZ is widely expressed in the rat and highly regulated by endogenous and exogenous GCs. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  7. Hydroclimatic control on suspended sediment dynamics of a regulated Alpine catchment: a conceptual approach

    Directory of Open Access Journals (Sweden)

    A. Costa

    2018-06-01

    Full Text Available We analyse the control of hydroclimatic factors on suspended sediment concentration (SSC in Alpine catchments by differentiating among the potential contributions of erosion and suspended sediment transport driven by erosive rainfall, defined as liquid precipitation over snow-free surfaces, ice melt from glacierized areas, and snowmelt on hillslopes. We account for the potential impact of hydropower by intercepting sediment fluxes originated in areas diverted to hydropower reservoirs, and by considering the contribution of hydropower releases to SSC. We obtain the hydroclimatic variables from daily gridded datasets of precipitation and temperature, implementing a degree-day model to simulate spatially distributed snow accumulation and snow–ice melt. We estimate hydropower releases by a conceptual approach with a unique virtual reservoir regulated on the basis of a target-volume function, representing normal reservoir operating conditions throughout a hydrological year. An Iterative Input Selection algorithm is used to identify the variables with the highest predictive power for SSC, their explained variance, and characteristic time lags. On this basis, we develop a hydroclimatic multivariate rating curve (HMRC which accounts for the contributions of the most relevant hydroclimatic input variables mentioned above. We calibrate the HMRC with a gradient-based nonlinear optimization method and we compare its performance with a traditional discharge-based rating curve. We apply the approach in the upper Rhône Basin, a large Swiss Alpine catchment heavily regulated by hydropower. Our results show that the three hydroclimatic processes – erosive rainfall, ice melt, and snowmelt – are significant predictors of mean daily SSC, while hydropower release does not have a significant explanatory power for SSC. The characteristic time lags of the hydroclimatic variables correspond to the typical flow concentration times of the basin. Despite not

  8. DMPD: The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10669111 The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. Qur...e The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. Authors Qur

  9. Variation in regulator of G-protein signaling 17 gene (RGS17 is associated with multiple substance dependence diagnoses

    Directory of Open Access Journals (Sweden)

    Zhang Huiping

    2012-05-01

    Full Text Available Abstract Background RGS17 and RGS20 encode two members of the regulator of G-protein signaling RGS-Rz subfamily. Variation in these genes may alter their transcription and thereby influence the function of G protein-coupled receptors, including opioid receptors, and modify risk for substance dependence. Methods The association of 13 RGS17 and eight RGS20 tag single nucleotide polymorphisms (SNPs was examined with four substance dependence diagnoses (alcohol (AD, cocaine (CD, opioid (OD or marijuana (MjD] in 1,905 African Americans (AAs: 1,562 cases and 343 controls and 1,332 European Americans (EAs: 981 cases and 351 controls. Analyses were performed using both χ2 tests and logistic regression analyses that covaried sex, age, and ancestry proportion. Correlation of genotypes and mRNA expression levels was assessed by linear regression analyses. Results Seven RGS17 SNPs showed a significant association with at least one of the four dependence traits after a permutation-based correction for multiple testing (0.003≤Pempirical≤0.037. The G allele of SNP rs596359, in the RGS17 promoter region, was associated with AD, CD, OD, or MjD in both populations (0.005≤Pempirical≤0.019. This allele was also associated with significantly lower mRNA expression levels of RGS17 in YRI subjects (P = 0.002 and non-significantly lower mRNA expression levels of RGS17 in CEU subjects (P = 0.185. No RGS20 SNPs were associated with any of the four dependence traits in either population. Conclusions This study demonstrated that variation in RGS17 was associated with risk for substance dependence diagnoses in both AA and EA populations.

  10. Comparative evolutionary diversity and phylogenetic structure across multiple forest dynamics plots: a mega-phylogeny approach

    Science.gov (United States)

    Erickson, David L.; Jones, Frank A.; Swenson, Nathan G.; Pei, Nancai; Bourg, Norman A.; Chen, Wenna; Davies, Stuart J.; Ge, Xue-jun; Hao, Zhanqing; Howe, Robert W.; Huang, Chun-Lin; Larson, Andrew J.; Lum, Shawn K. Y.; Lutz, James A.; Ma, Keping; Meegaskumbura, Madhava; Mi, Xiangcheng; Parker, John D.; Fang-Sun, I.; Wright, S. Joseph; Wolf, Amy T.; Ye, W.; Xing, Dingliang; Zimmerman, Jess K.; Kress, W. John

    2014-01-01

    Forest dynamics plots, which now span longitudes, latitudes, and habitat types across the globe, offer unparalleled insights into the ecological and evolutionary processes that determine how species are assembled into communities. Understanding phylogenetic relationships among species in a community has become an important component of assessing assembly processes. However, the application of evolutionary information to questions in community ecology has been limited in large part by the lack of accurate estimates of phylogenetic relationships among individual species found within communities, and is particularly limiting in comparisons between communities. Therefore, streamlining and maximizing the information content of these community phylogenies is a priority. To test the viability and advantage of a multi-community phylogeny, we constructed a multi-plot mega-phylogeny of 1347 species of trees across 15 forest dynamics plots in the ForestGEO network using DNA barcode sequence data (rbcL, matK, and psbA-trnH) and compared community phylogenies for each individual plot with respect to support for topology and branch lengths, which affect evolutionary inference of community processes. The levels of taxonomic differentiation across the phylogeny were examined by quantifying the frequency of resolved nodes throughout. In addition, three phylogenetic distance (PD) metrics that are commonly used to infer assembly processes were estimated for each plot [PD, Mean Phylogenetic Distance (MPD), and Mean Nearest Taxon Distance (MNTD)]. Lastly, we examine the partitioning of phylogenetic diversity among community plots through quantification of inter-community MPD and MNTD. Overall, evolutionary relationships were highly resolved across the DNA barcode-based mega-phylogeny, and phylogenetic resolution for each community plot was improved when estimated within the context of the mega-phylogeny. Likewise, when compared with phylogenies for individual plots, estimates of

  11. DMPD: Toll-like receptors regulation of viral infection and disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18280610 Toll-like receptors regulation of viral infection and disease. Thompson JM...how Toll-like receptors regulation of viral infection and disease. PubmedID 18280610 Title Toll-like recepto...rs regulation of viral infection and disease. Authors Thompson JM, Iwasaki A. Pub

  12. DMPD: Regulation of mitochondrial antiviral signaling pathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18549796 Regulation of mitochondrial antiviral signaling pathways. Moore CB, Ting J...P. Immunity. 2008 Jun;28(6):735-9. (.png) (.svg) (.html) (.csml) Show Regulation of mitochondrial antiviral ...signaling pathways. PubmedID 18549796 Title Regulation of mitochondrial antiviral signaling pathways. Author

  13. DMPD: Innate immune recognition of, and regulation by, DNA. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16979939 Innate immune recognition of, and regulation by, DNA. Ishii KJ, Akira S. T...rends Immunol. 2006 Nov;27(11):525-32. Epub 2006 Sep 18. (.png) (.svg) (.html) (.csml) Show Innate immune recognition... of, and regulation by, DNA. PubmedID 16979939 Title Innate immune recognition of, and regulation b

  14. DMPD: Innate immune responses: crosstalk of signaling and regulation of genetranscription. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 16753195 Innate immune responses: crosstalk of signaling and regulation of genetran...l) (.csml) Show Innate immune responses: crosstalk of signaling and regulation of genetranscription. PubmedI...D 16753195 Title Innate immune responses: crosstalk of signaling and regulation o

  15. DMPD: Negative regulation of cytoplasmic RNA-mediated antiviral signaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18703349 Negative regulation of cytoplasmic RNA-mediated antiviral signaling. Komur...Show Negative regulation of cytoplasmic RNA-mediated antiviral signaling. PubmedID 18703349 Title Negative r...egulation of cytoplasmic RNA-mediated antiviral signaling. Authors Komuro A, Bamm

  16. DMPD: Regulation of endogenous apolipoprotein E secretion by macrophages. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 18388328 Regulation of endogenous apolipoprotein E secretion by macrophages. Kockx ...svg) (.html) (.csml) Show Regulation of endogenous apolipoprotein E secretion by macrophages. PubmedID 18388...328 Title Regulation of endogenous apolipoprotein E secretion by macrophages. Aut

  17. DMPD: Iron regulation of hepatic macrophage TNFalpha expression. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 11841920 Iron regulation of hepatic macrophage TNFalpha expression. Tsukamoto H. Fr...ee Radic Biol Med. 2002 Feb 15;32(4):309-13. (.png) (.svg) (.html) (.csml) Show Iron regulation of hepatic macrophage... TNFalpha expression. PubmedID 11841920 Title Iron regulation of hepatic macrophage TNFalpha expres

  18. DMPD: Post-transcriptional regulation of proinflammatory proteins. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 15075353 Post-transcriptional regulation of proinflammatory proteins. Anderson P, P...l) (.csml) Show Post-transcriptional regulation of proinflammatory proteins. PubmedID 15075353 Title Post-tr...anscriptional regulation of proinflammatory proteins. Authors Anderson P, Phillip

  19. DMPD: Regulation of cytokine signaling by SOCS family molecules. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 14644140 Regulation of cytokine signaling by SOCS family molecules. Fujimoto M, Nak...a T. Trends Immunol. 2003 Dec;24(12):659-66. (.png) (.svg) (.html) (.csml) Show Regulation of cytokine signaling by SOCS family... molecules. PubmedID 14644140 Title Regulation of cytokine signaling by SOCS family molec

  20. DMPD: The SAP family of adaptors in immune regulation. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 15541655 The SAP family of adaptors in immune regulation. Latour S, Veillette A. Se...min Immunol. 2004 Dec;16(6):409-19. (.png) (.svg) (.html) (.csml) Show The SAP family of adaptors in immune ...regulation. PubmedID 15541655 Title The SAP family of adaptors in immune regulation. Authors Latour S, Veill

  1. DMPD: New insights into the regulation of TLR signaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16698941 New insights into the regulation of TLR signaling. Miggin SM, O'Neill LA. ...J Leukoc Biol. 2006 Aug;80(2):220-6. Epub 2006 May 12. (.png) (.svg) (.html) (.csml) Show New insights into ...the regulation of TLR signaling. PubmedID 16698941 Title New insights into the regulation of TLR signaling.

  2. DMPD: Interferon gene regulation: not all roads lead to Tolls. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16095970 Interferon gene regulation: not all roads lead to Tolls. Jefferies CA, Fit...zgerald KA. Trends Mol Med. 2005 Sep;11(9):403-11. (.png) (.svg) (.html) (.csml) Show Interferon gene regulation: not all roads... lead to Tolls. PubmedID 16095970 Title Interferon gene regulation: not all roads lead to

  3. Dynamic evolution of Geranium mitochondrial genomes through multiple horizontal and intracellular gene transfers.

    Science.gov (United States)

    Park, Seongjun; Grewe, Felix; Zhu, Andan; Ruhlman, Tracey A; Sabir, Jamal; Mower, Jeffrey P; Jansen, Robert K

    2015-10-01

    The exchange of genetic material between cellular organelles through intracellular gene transfer (IGT) or between species by horizontal gene transfer (HGT) has played an important role in plant mitochondrial genome evolution. The mitochondrial genomes of Geraniaceae display a number of unusual phenomena including highly accelerated rates of synonymous substitutions, extensive gene loss and reduction in RNA editing. Mitochondrial DNA sequences assembled for 17 species of Geranium revealed substantial reduction in gene and intron content relative to the ancestor of the Geranium lineage. Comparative analyses of nuclear transcriptome data suggest that a number of these sequences have been functionally relocated to the nucleus via IGT. Evidence for rampant HGT was detected in several Geranium species containing foreign organellar DNA from diverse eudicots, including many transfers from parasitic plants. One lineage has experienced multiple, independent HGT episodes, many of which occurred within the past 5.5 Myr. Both duplicative and recapture HGT were documented in Geranium lineages. The mitochondrial genome of Geranium brycei contains at least four independent HGT tracts that are absent in its nearest relative. Furthermore, G. brycei mitochondria carry two copies of the cox1 gene that differ in intron content, providing insight into contrasting hypotheses on cox1 intron evolution. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  4. Complex Dynamics in a Triopoly Game with Multiple Delays in the Competition of Green Product Level

    Science.gov (United States)

    Si, Fengshan; Ma, Junhai

    Research on the output game behavior of oligopoly has greatly advanced in recent years. But many unknowns remain, particularly the influence of consumers’ willingness to buy green products on the oligopoly output game. This paper constructs a triopoly output game model with multiple delays in the competition of green products. The influence of the parameters on the stability and complexity of the system is studied by analyzing the existence and local asymptotic stability of the equilibrium point. It is found that the system loses stability and increases complexity if delay parameters exceed a certain range. In the unstable or chaotic game market, the decisions of oligopoly will be counterproductive. It is also observed that the influence of weight and output adjustment speed on the firm itself is obviously stronger than the influence of other firms. In addition, it is important that weight and output adjustment speed cannot increase indefinitely, otherwise it will bring unnecessary losses to the firm. Finally, chaos control is realized by using the variable feedback control method. The research results of this paper can provide a reference for decision-making for the output of the game of oligopoly.

  5. Improvement of MARS code through the removal of bit-packed words and multiple use of DLLs (Dynamic Link Library)

    Energy Technology Data Exchange (ETDEWEB)

    Jung, B. D.; Jung, J. J.; Ha, K. S.; Hwang, M. K.; Lee, Y. S.; Lee, W. J. [KAERI, Taejon (Korea, Republic of)

    1999-10-01

    The readability of MARS code has been enhanced greatly by replacing the bit-packed word with several logical words and integer words and recoding the related subroutines, which have the complicated bit operations and packed words. Functional improvements of code has been achieved through the multiple uses of dynamic link libraries(DLL) for containment analysis module CONTEMPT4 and multidimensional kinetics analysis module MASTER. The establishment of integrated analysis system, MARS/CONTEMPT/MASTER, was validated through the verification calculation for a postulated problem. MARS user-friendly features are also improved by displaying the 2D contour map of 3 D module data on-line. In addition to the on-line-graphics, the MARS windows menus were upgraded to include the on-line-manual, pre-view of input and output, and link to MARS web site. As a result, the readability, applicability, and user-friendly features of MARS code has been greatly enhanced.

  6. Improvement of MARS code through the removal of bit-packed words and multiple use of DLLs (Dynamic Link Library)

    International Nuclear Information System (INIS)

    Jung, B. D.; Jung, J. J.; Ha, K. S.; Hwang, M. K.; Lee, Y. S.; Lee, W. J.

    1999-01-01

    The readability of MARS code has been enhanced greatly by replacing the bit-packed word with several logical words and integer words and recoding the related subroutines, which have the complicated bit operations and packed words. Functional improvements of code has been achieved through the multiple uses of dynamic link libraries(DLL) for containment analysis module CONTEMPT4 and multidimensional kinetics analysis module MASTER. The establishment of integrated analysis system, MARS/CONTEMPT/MASTER, was validated through the verification calculation for a postulated problem. MARS user-friendly features are also improved by displaying the 2D contour map of 3 D module data on-line. In addition to the on-line-graphics, the MARS windows menus were upgraded to include the on-line-manual, pre-view of input and output, and link to MARS web site. As a result, the readability, applicability, and user-friendly features of MARS code has been greatly enhanced

  7. Dynamic analysis of optical soliton pair and four-wave mixing via Fano interference in multiple quantum wells

    International Nuclear Information System (INIS)

    Yan, Wei; Qu, Junle; Niu, H B

    2014-01-01

    We perform a time-dependent analysis of the formation and stable propagation of an ultraslow optical soliton pair, and four-wave mixing (FWM) via tunable Fano interference in double-cascade type semiconductor multiple quantum wells (SMQWs). By using the probability amplitude method to describe the interaction of the system, we demonstrate that the electromagnetically induced transparency (EIT) can be controlled by Fano interference in the linear case and the strength of Fano interference has an important effect on the group velocity and amplitude of the soliton pair in the nonlinear case. Then, when the signal field is removed, the dynamic FWM process is analyzed in detail, and we find that the strength of Fano interference also has an important effect on the FWM’s efficiency: the maximum FWM efficiency is ∼28% in appropriate conditions. The investigations are promising for practical applications in optical devices and optical information processing for solid systems. (paper)

  8. Multiple equilibria on planet Dune: climate–vegetation dynamics on a sandy planet

    Directory of Open Access Journals (Sweden)

    Fabio Cresto Aleina

    2013-01-01

    Full Text Available We study the interaction between climate and vegetation on an ideal water-limited planet, focussing on the influence of vegetation on the global water cycle. We introduce a simple mechanistic box model consisting in a two-layer representation of the atmosphere and a two-layer soil scheme. The model includes the dynamics of vegetation cover, and the main physical processes of energy and water exchange among the different components. With a realistic choice of parameters, this model displays three stable equilibria, depending on the initial conditions of soil water and vegetation cover. The system reaches a hot and dry state for low values of initial water content and/or vegetation cover, while we observe a wet, vegetated state with mild surface temperature when the system starts from larger initial values of both variables. The third state is a cold desert, where plants transfer enough water to the atmosphere to start a weaker, evaporation-dominated water cycle before they wilt. These results indicate that in this system vegetation plays a central role in transferring water from the soil to the atmosphere and trigger a hydrologic cycle. The model adopted here can also be used to conceptually illustrate processes and feedbacks affecting the water cycle in water-limited continental areas on Earth.

  9. Utilizing multiple state variables to improve the dynamic range of analog switching in a memristor

    International Nuclear Information System (INIS)

    Jeong, YeonJoo; Kim, Sungho; Lu, Wei D.

    2015-01-01

    Memristors and memristive systems have been extensively studied for data storage and computing applications such as neuromorphic systems. To act as synapses in neuromorphic systems, the memristor needs to exhibit analog resistive switching (RS) behavior with incremental conductance change. In this study, we show that the dynamic range of the analog RS behavior can be significantly enhanced in a tantalum-oxide-based memristor. By controlling different state variables enabled by different physical effects during the RS process, the gradual filament expansion stage can be selectively enhanced without strongly affecting the abrupt filament length growth stage. Detailed physics-based modeling further verified the observed experimental effects and revealed the roles of oxygen vacancy drift and diffusion processes, and how the diffusion process can be selectively enhanced during the filament expansion stage. These findings lead to more desirable and reliable memristor behaviors for analog computing applications. Additionally, the ability to selectively control different internal physical processes demonstrated in the current study provides guidance for continued device optimization of memristor devices in general

  10. Examining the Dynamic Structure of Daily Internalizing and Externalizing Behavior at Multiple Levels of Analysis

    Directory of Open Access Journals (Sweden)

    Aidan G.C. Wright

    2015-12-01

    Full Text Available Psychiatric diagnostic covariation suggests that the underlying structure of psychopathology is not one of circumscribed disorders. Quantitative modeling of individual differences in diagnostic patterns has uncovered several broad domains of mental disorder liability, of which the Internalizing and Externalizing spectra have garnered the greatest support. These dimensions have generally been estimated from lifetime or past-year comorbidity patters, which are distal from the covariation of symptoms and maladaptive behavior that ebb and flow in daily life. In this study, structural models are applied to daily diary data (Median = 94 days of maladaptive behaviors collected from a sample (N = 101 of individuals diagnosed with personality disorders. Using multilevel and unified structural equation modeling, between-person, within-person, and person-specific structures were estimated from 16 behaviors that are encompassed by the Internalizing and Externalizing spectra. At the between-person level (i.e., individual differences in average endorsement across days we found support for a two-factor Internalizing-Externalizing model, which exhibits significant associations with corresponding diagnostic spectra. At the within-person level (i.e., dynamic covariation among daily behavior pooled across individuals we found support for a more differentiated, four-factor, Negative Affect-Detachment-Hostility-Impulsivity structure. Finally, we demonstrate that the person-specific structures of associations between these four domains are highly idiosyncratic.

  11. Examining the Dynamic Structure of Daily Internalizing and Externalizing Behavior at Multiple Levels of Analysis

    Science.gov (United States)

    Wright, Aidan G. C.; Beltz, Adriene M.; Gates, Kathleen M.; Molenaar, Peter C. M.; Simms, Leonard J.

    2015-01-01

    Psychiatric diagnostic covariation suggests that the underlying structure of psychopathology is not one of circumscribed disorders. Quantitative modeling of individual differences in diagnostic patterns has uncovered several broad domains of mental disorder liability, of which the Internalizing and Externalizing spectra have garnered the greatest support. These dimensions have generally been estimated from lifetime or past-year comorbidity patters, which are distal from the covariation of symptoms and maladaptive behavior that ebb and flow in daily life. In this study, structural models are applied to daily diary data (Median = 94 days) of maladaptive behaviors collected from a sample (N = 101) of individuals diagnosed with personality disorders (PDs). Using multilevel and unified structural equation modeling, between-person, within-person, and person-specific structures were estimated from 16 behaviors that are encompassed by the Internalizing and Externalizing spectra. At the between-person level (i.e., individual differences in average endorsement across days) we found support for a two-factor Internalizing–Externalizing model, which exhibits significant associations with corresponding diagnostic spectra. At the within-person level (i.e., dynamic covariation among daily behavior pooled across individuals) we found support for a more differentiated, four-factor, Negative Affect-Detachment-Hostility-Disinhibition structure. Finally, we demonstrate that the person-specific structures of associations between these four domains are highly idiosyncratic. PMID:26732546

  12. The impact of multiple information on coupled awareness-epidemic dynamics in multiplex networks

    Science.gov (United States)

    Pan, Yaohui; Yan, Zhijun

    2018-02-01

    Growing interest has emerged in the study of the interplay between awareness and epidemics in multiplex networks. However, previous studies on this issue usually assume that all aware individuals take the same level of precautions, ignoring individual heterogeneity. In this paper, we investigate the coupled awareness-epidemic dynamics in multiplex networks considering individual heterogeneity. Here, the precaution levels are heterogeneous and depend on three types of information: contact information and local and global prevalence information. The results show that contact-based precautions can decrease the epidemic prevalence and augment the epidemic threshold, but prevalence-based precautions, regardless of local or global information, can only decrease the epidemic prevalence. Moreover, unlike previous studies in single-layer networks, we do not find a greater impact of local prevalence information on the epidemic prevalence compared to global prevalence information. In addition, we find that the altruistic behaviors of infected individuals can effectively suppress epidemic spreading, especially when the level of contact-based precaution is high.

  13. Multiple degree of freedom inverted pendulum dynamics: Modeling, computation, and experimentation

    Science.gov (United States)

    Chen, Cheng-Yuan Jerry

    A pendulum is statically unstable in its upright inverted state due to the Earth's gravitational attraction which points downward. However, with proper forcing, the pendulum can be stabilized in its upright inverted state. Special interest is on periodic vertical forcing applied to the pendulum's base to stabilize it around the upright inverted equilibrium. Many researchers have studied how to stabilize the system by varying various parameters, in particular its amplitude and frequency. Most have focused on the single degree of freedom inverted pendulum case, which with linear assumption can be described via Mathieu's equation. The system stability can then be characterized by Floquet theory. Our focus is on searching for the periodic solutions inside the linearly stable region of the pendulum's inverted state when the pendulum is under proper periodic forcing. Our research shows that under appropriate excitation by controlling the forcing amplitude and frequency, the pendulum can maintain certain periodic orbits around its inverted state which we characterize in a systematic way. In this thesis, we applied four different kinds of geometric realizations of the system response: system time traces, system phase portraits, three dimensional views of the system phase portrait as a function of input forcing, and the system's power spectral density diagram. By analyzing these four diagrams simultaneously, we characterize different kinds of multi-frequency periodic behavior around the pendulum's inverted state. To further discuss the effect of the nonlinearity, we applied perturbation techniques using the normalized forcing amplitude as a perturbation parameter to carry out the approximate periodic solutions on a single degree of freedom inverted pendulum nonlinear model. We also discuss the multiple degree of freedom inverted pendulum system. Both numerical simulation and experiments were performed and detailed comparisons are discussed. Our numerical simulations show

  14. Expressions of multiple neuronal dynamics during sensorimotor learning in the motor cortex of behaving monkeys.

    Directory of Open Access Journals (Sweden)

    Yael Mandelblat-Cerf

    Full Text Available Previous studies support the notion that sensorimotor learning involves multiple processes. We investigated the neuronal basis of these processes by recording single-unit activity in motor cortex of non-human primates (Macaca fascicularis, during adaptation to force-field perturbations. Perturbed trials (reaching to one direction were practiced along with unperturbed trials (to other directions. The number of perturbed trials relative to the unperturbed ones was either low or high, in two separate practice schedules. Unsurprisingly, practice under high-rate resulted in faster learning with more pronounced generalization, as compared to the low-rate practice. However, generalization and retention of behavioral and neuronal effects following practice in high-rate were less stable; namely, the faster learning was forgotten faster. We examined two subgroups of cells and showed that, during learning, the changes in firing-rate in one subgroup depended on the number of practiced trials, but not on time. In contrast, changes in the second subgroup depended on time and practice; the changes in firing-rate, following the same number of perturbed trials, were larger under high-rate than low-rate learning. After learning, the neuronal changes gradually decayed. In the first subgroup, the decay pace did not depend on the practice rate, whereas in the second subgroup, the decay pace was greater following high-rate practice. This group shows neuronal representation that mirrors the behavioral performance, evolving faster but also decaying faster at learning under high-rate, as compared to low-rate. The results suggest that the stability of a new learned skill and its neuronal representation are affected by the acquisition schedule.

  15. Application of multiple geochemical markers to investigate organic pollution in a dynamic coastal zone.

    Science.gov (United States)

    Liu, Liang-Ying; Wang, Ji-Zhong; Wong, Charles S; Qiu, Jian-Wen; Zeng, Eddy Y

    2013-02-01

    Multiple geochemical markers, including aliphatic hydrocarbons (n-alkanes), linear alkylbenzenes (LABs), and polycyclic aromatic hydrocarbons (PAHs), were employed to relate sediment organic chemical pollution in the coastal zone off South China to socioeconomic development there. Concentrations of Σn-C(15-35) (n-alkanes with 15-35 carbon atoms), ΣLAB (sum of C(10) to C(13) LABs), and Σ(26) PAH (sum of 26 PAH compounds) ranged from 110 to 3,160, 11 to 160, and 26 to 600 ng/g, with medians of 730, 40, and 230 ng/g, respectively. Natural hydrocarbons were mainly derived from terrestrial higher plant waxes, and in minor amounts from aquatic plankton and bacteria. Compositions of LABs indicated that considerable amounts of poorly treated wastewater had been directly discharged or transported to the eastern and western coastal areas of Guangdong Province. In addition, anthropogenic hydrocarbons were derived largely from vehicular emissions and combustion of domestic coal and biomass and to a lesser extent from oil spills. Eastern and western coastal sediments contained higher levels of LABs but lower levels of PAHs than those of the Pearl River Estuary, a coastal area of the Pearl River Delta. This spatial pattern of organic pollution was consistent with chemical use patterns. The eastern and western regions of Guangdong Province are economically less developed than the Pearl River Delta region, where more domestic wastewater treatment plants have been built. However, greater amounts of energy are consumed in the latter region to produce more combustion-derived PAH contamination. Copyright © 2012 SETAC.

  16. Dynamics of habitat selection in birds: adaptive response to nest predation depends on multiple factors.

    Science.gov (United States)

    Devries, J H; Clark, R G; Armstrong, L M

    2018-05-01

    According to theory, habitat selection by organisms should reflect underlying habitat-specific fitness consequences and, in birds, reproductive success has a strong impact on population growth in many species. Understanding processes affecting habitat selection also is critically important for guiding conservation initiatives. Northern pintails (Anas acuta) are migratory, temperate-nesting birds that breed in greatest concentrations in the prairies of North America and their population remains below conservation goals. Habitat loss and changing land use practices may have decoupled formerly reliable fitness cues with respect to nest habitat choices. We used data from 62 waterfowl nesting study sites across prairie Canada (1997-2009) to examine nest survival, a primary fitness metric, at multiple scales, in combination with estimates of habitat selection (i.e., nests versus random points), to test for evidence of adaptive habitat choices. We used the same habitat covariates in both analyses. Pintail nest survival varied with nest initiation date, nest habitat, pintail breeding pair density, landscape composition and annual moisture. Selection of nesting habitat reflected patterns in nest survival in some cases, indicating adaptive selection, but strength of habitat selection varied seasonally and depended on population density and landscape composition. Adaptive selection was most evident late in the breeding season, at low breeding densities and in cropland-dominated landscapes. Strikingly, at high breeding density, habitat choice appears to become maladaptive relative to nest predation. At larger spatial scales, the relative availability of habitats with low versus high nest survival, and changing land use practices, may limit the reproductive potential of pintails.

  17. A Novel Randomized Search Technique for Multiple Mobile Robot Paths Planning In Repetitive Dynamic Environment

    Directory of Open Access Journals (Sweden)

    Vahid Behravesh

    2012-08-01

    Full Text Available Presented article is studying the issue of path navigating for numerous robots. Our presented approach is based on both priority and the robust method for path finding in repetitive dynamic. Presented model can be generally implementable and useable: We do not assume any restriction regarding the quantity of levels of freedom for robots, and robots of diverse kinds can be applied at the same time. We proposed a random method and hill-climbing technique in the area based on precedence plans, which is used to determine a solution to a given trajectory planning problem and to make less the extent of total track. Our method plans trajectories for particular robots in the setting-time scope. Therefore, in order to specifying the interval of constant objects similar to other robots and the extent of the tracks which is traversed. For measuring the hazard for robots to conflict with each other it applied a method based on probability of the movements of robots. This algorithm applied to real robots with successful results. The proposed method performed and judged on both real robots and in simulation. We performed sequence of100tests with 8 robots for comparing with coordination method and current performances are effective. However, maximizing the performance is still possible. These performances estimations performed on Windows operating system and 3GHz Intel Pentium IV with and compiles with GCC 3.4. We used our PCGA robot for all experiments.  For a large environment of 19×15m2where we accomplished 40tests, our model is competent to plan high-quality paths in a severely short time (less than a second. Moreover, this article utilized lookup tables to keep expenses the formerly navigated robots made, increasing the number of robots don’t expand computation time.

  18. Investigating water budget dynamics in 18 river basins across the Tibetan Plateau through multiple datasets

    Science.gov (United States)

    Liu, Wenbin; Sun, Fubao; Li, Yanzhong; Zhang, Guoqing; Sang, Yan-Fang; Lim, Wee Ho; Liu, Jiahong; Wang, Hong; Bai, Peng

    2018-01-01

    The dynamics of basin-scale water budgets over the Tibetan Plateau (TP) are not well understood nowadays due to the lack of in situ hydro-climatic observations. In this study, we investigate the seasonal cycles and trends of water budget components (e.g. precipitation P, evapotranspiration ET and runoff Q) in 18 TP river basins during the period 1982-2011 through the use of multi-source datasets (e.g. in situ observations, satellite retrievals, reanalysis outputs and land surface model simulations). A water balance-based two-step procedure, which considers the changes in basin-scale water storage on the annual scale, is also adopted to calculate actual ET. The results indicated that precipitation (mainly snowfall from mid-autumn to next spring), which are mainly concentrated during June-October (varied among different monsoons-impacted basins), was the major contributor to the runoff in TP basins. The P, ET and Q were found to marginally increase in most TP basins during the past 30 years except for the upper Yellow River basin and some sub-basins of Yalong River, which were mainly affected by the weakening east Asian monsoon. Moreover, the aridity index (PET/P) and runoff coefficient (Q/P) decreased slightly in most basins, which were in agreement with the warming and moistening climate in the Tibetan Plateau. The results obtained demonstrated the usefulness of integrating multi-source datasets to hydrological applications in the data-sparse regions. More generally, such an approach might offer helpful insights into understanding the water and energy budgets and sustainability of water resource management practices of data-sparse regions in a changing environment.

  19. Towards methodical modelling: Differences between the structure and output dynamics of multiple conceptual models

    Science.gov (United States)

    Knoben, Wouter; Woods, Ross; Freer, Jim

    2016-04-01

    Conceptual hydrologic models consist of a certain arrangement of spatial and temporal dynamics consisting of stores, fluxes and transformation functions, depending on the modeller's choices and intended use. They have the advantages of being computationally efficient, being relatively easy model structures to reconfigure and having relatively low input data demands. This makes them well-suited for large-scale and large-sample hydrology, where appropriately representing the dominant hydrologic functions of a catchment is a main concern. Given these requirements, the number of parameters in the model cannot be too high, to avoid equifinality and identifiability issues. This limits the number and level of complexity of dominant hydrologic processes the model can represent. Specific purposes and places thus require a specific model and this has led to an abundance of conceptual hydrologic models. No structured overview of these models exists and there is no clear method to select appropriate model structures for different catchments. This study is a first step towards creating an overview of the elements that make up conceptual models, which may later assist a modeller in finding an appropriate model structure for a given catchment. To this end, this study brings together over 30 past and present conceptual models. The reviewed model structures are simply different configurations of three basic model elements (stores, fluxes and transformation functions), depending on the hydrologic processes the models are intended to represent. Differences also exist in the inner workings of the stores, fluxes and transformations, i.e. the mathematical formulations that describe each model element's intended behaviour. We investigate the hypothesis that different model structures can produce similar behavioural simulations. This can clarify the overview of model elements by grouping elements which are similar, which can improve model structure selection.

  20. THE LONG-TERM DYNAMICAL EVOLUTION OF DISK-FRAGMENTED MULTIPLE SYSTEMS IN THE SOLAR NEIGHBORHOOD

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yun [Department of Astronomy, School of Physics, Peking University, Yiheyuan Lu 5, Haidian Qu, Beijing 100871 (China); Kouwenhoven, M. B. N. [Department of Mathematical Sciences, Xi’an Jiaotong-Liverpool University, 111 Ren’ai Road, Suzhou Dushu Lake Science and Education Innovation District, Suzhou Industrial Park, Suzhou 215123 (China); Stamatellos, D. [Jeremiah Horrocks Institute for Mathematics, Physics and Astronomy, University of Central Lancashire, Preston PR1 2HE (United Kingdom); Goodwin, Simon P., E-mail: t.kouwenhoven@xjtlu.edu.cn [Department of Physics and Astronomy, The University of Sheffield, Hicks Building, Hounsfield Road, Sheffield S3 7RH (United Kingdom)

    2016-11-10

    The origin of very low-mass hydrogen-burning stars, brown dwarfs (BDs), and planetary-mass objects (PMOs) at the low-mass end of the initial mass function is not yet fully understood. Gravitational fragmentation of circumstellar disks provides a possible mechanism for the formation of such low-mass objects. The kinematic and binary properties of very low-mass objects formed through disk fragmentation at early times (<10 Myr) were discussed in our previous paper. In this paper we extend the analysis by following the long-term evolution of disk-fragmented systems up to an age of 10 Gyr, covering the ages of the stellar and substellar populations in the Galactic field. We find that the systems continue to decay, although the rates at which companions escape or collide with each other are substantially lower than during the first 10 Myr, and that dynamical evolution is limited beyond 1 Gyr. By t = 10 Gyr, about one third of the host stars are single, and more than half have only one companion left. Most of the other systems have two companions left that orbit their host star in widely separated orbits. A small fraction of companions have formed binaries that orbit the host star in a hierarchical triple configuration. The majority of such double-companion systems have internal orbits that are retrograde with respect to their orbits around their host stars. Our simulations allow a comparison between the predicted outcomes of disk fragmentation with the observed low-mass hydrogen-burning stars, BDs, and PMOs in the solar neighborhood. Imaging and radial velocity surveys for faint binary companions among nearby stars are necessary for verification or rejection of the formation mechanism proposed in this paper.

  1. Dynamic Regulation of Circulating microRNAs During Acute Exercise and Long-Term Exercise Training in Basketball Athletes

    OpenAIRE

    Yongqin Li; Mengchao Yao; Qiulian Zhou; Yan Cheng; Lin Che; Jiahong Xu; Junjie Xiao; Zhongming Shen; Yihua Bei

    2018-01-01

    Emerging evidence indicates the beneficial effects of physical exercise on human health, which depends on the intensity, training time, exercise type, environmental factors, and the personal health status. Conventional biomarkers provide limited insight into the exercise-induced adaptive processes. Circulating microRNAs (miRNAs, miRs) are dynamically regulated in response to acute exhaustive exercise and sustained rowing, running and cycling exercises. However, circulating miRNAs in response ...

  2. New Evidence for the Dynamical Decay of a Multiple System in the Orion Kleinmann–Low Nebula

    Energy Technology Data Exchange (ETDEWEB)

    Luhman, K. L. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); Robberto, M.; Gabellini, M. Giulia Ubeira; Ubeda, L. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Tan, J. C. [Department of Astronomy, University of Florida, Gainesville, FL 32611 (United States); Andersen, M. [Gemini Observatory, Casilla 603, La Serena (Chile); Manara, C. F. [Scientific Support Office, Directorate of Science, European Space Research and Technology Centre, Keplerlaan 1, NL-2201 AZ Noordwijk (Netherlands); Platais, I., E-mail: kluhman@astro.psu.edu [Johns Hopkins University, Department of Physics and Astronomy, 3400 North Charles Street, Baltimore, MD 21218 (United States)

    2017-03-20

    We have measured astrometry for members of the Orion Nebula Cluster with images obtained in 2015 with the Wide Field Camera 3 on board the Hubble Space Telescope . By comparing those data to previous measurements with the Near-Infrared Camera and Multi-Object Spectrometer on Hubble in 1998, we have discovered that a star in the Kleinmann–Low Nebula, source x from Lonsdale et al., is moving with an unusually high proper motion of 29 mas yr{sup −1}, which corresponds to 55 km s{sup −1} at the distance of Orion. Previous radio observations have found that three other stars in the Kleinmann–Low Nebula (the Becklin–Neugebauer object and sources I and n) have high proper motions (5–14 mas yr{sup −1}) and were near a single location ∼540 years ago, and thus may have been members of a multiple system that dynamically decayed. The proper motion of source x is consistent with ejection from that same location 540 years ago, which provides strong evidence that the dynamical decay did occur and that the runaway star BN originated in the Kleinmann–Low Nebula rather than the nearby Trapezium cluster. However, our constraint on the motion of source n is significantly smaller than the most recent radio measurement, which indicates that it did not participate in the event that ejected the other three stars.

  3. Modeling the Potential Effects of New Tobacco Products and Policies: A Dynamic Population Model for Multiple Product Use and Harm

    Science.gov (United States)

    Vugrin, Eric D.; Rostron, Brian L.; Verzi, Stephen J.; Brodsky, Nancy S.; Brown, Theresa J.; Choiniere, Conrad J.; Coleman, Blair N.; Paredes, Antonio; Apelberg, Benjamin J.

    2015-01-01

    Background Recent declines in US cigarette smoking prevalence have coincided with increases in use of other tobacco products. Multiple product tobacco models can help assess the population health impacts associated with use of a wide range of tobacco products. Methods and Findings We present a multi-state, dynamical systems population structure model that can be used to assess the effects of tobacco product use behaviors on population health. The model incorporates transition behaviors, such as initiation, cessation, switching, and dual use, related to the use of multiple products. The model tracks product use prevalence and mortality attributable to tobacco use for the overall population and by sex and age group. The model can also be used to estimate differences in these outcomes between scenarios by varying input parameter values. We demonstrate model capabilities by projecting future cigarette smoking prevalence and smoking-attributable mortality and then simulating the effects of introduction of a hypothetical new lower-risk tobacco product under a variety of assumptions about product use. Sensitivity analyses were conducted to examine the range of population impacts that could occur due to differences in input values for product use and risk. We demonstrate that potential benefits from cigarette smokers switching to the lower-risk product can be offset over time through increased initiation of this product. Model results show that population health benefits are particularly sensitive to product risks and initiation, switching, and dual use behaviors. Conclusion Our model incorporates the variety of tobacco use behaviors and risks that occur with multiple products. As such, it can evaluate the population health impacts associated with the introduction of new tobacco products or policies that may result in product switching or dual use. Further model development will include refinement of data inputs for non-cigarette tobacco products and inclusion of health

  4. Bidirectional coupling between astrocytes and neurons mediates learning and dynamic coordination in the brain: a multiple modeling approach.

    Directory of Open Access Journals (Sweden)

    John J Wade

    Full Text Available In recent years research suggests that astrocyte networks, in addition to nutrient and waste processing functions, regulate both structural and synaptic plasticity. To understand the biological mechanisms that underpin such plasticity requires the development of cell level models that capture the mutual interaction between astrocytes and neurons. This paper presents a detailed model of bidirectional signaling between astrocytes and neurons (the astrocyte-neuron model or AN model which yields new insights into the computational role of astrocyte-neuronal coupling. From a set of modeling studies we demonstrate two significant findings. Firstly, that spatial signaling via astrocytes can relay a "learning signal" to remote synaptic sites. Results show that slow inward currents cause synchronized postsynaptic activity in remote neurons and subsequently allow Spike-Timing-Dependent Plasticity based learning to occur at the associated synapses. Secondly, that bidirectional communication between neurons and astrocytes underpins dynamic coordination between neuron clusters. Although our composite AN model is presently applied to simplified neural structures and limited to coordination between localized neurons, the principle (which embodies structural, functional and dynamic complexity, and the modeling strategy may be extended to coordination among remote neuron clusters.

  5. Surface dynamics in allosteric regulation of protein-protein interactions: modulation of calmodulin functions by Ca2+.

    Directory of Open Access Journals (Sweden)

    Yosef Y Kuttner

    2013-04-01

    Full Text Available Knowledge of the structural basis of protein-protein interactions (PPI is of fundamental importance for understanding the organization and functioning of biological networks and advancing the design of therapeutics which target PPI. Allosteric modulators play an important role in regulating such interactions by binding at site(s orthogonal to the complex interface and altering the protein's propensity for complex formation. In this work, we apply an approach recently developed by us for analyzing protein surfaces based on steered molecular dynamics simulation (SMD to the study of the dynamic properties of functionally distinct conformations of a model protein, calmodulin (CaM, whose ability to interact with target proteins is regulated by the presence of the allosteric modulator Ca(2+. Calmodulin is a regulatory protein that acts as an intracellular Ca(2+ sensor to control a wide variety of cellular processes. We demonstrate that SMD analysis is capable of pinpointing CaM surfaces implicated in the recognition of both the allosteric modulator Ca(2+ and target proteins. Our analysis of changes in the dynamic properties of the CaM backbone elicited by Ca(2+ binding yielded new insights into the molecular mechanism of allosteric regulation of CaM-target interactions.

  6. A dynamic model-based estimate of the value of a vanadium redox flow battery for frequency regulation in Texas

    International Nuclear Information System (INIS)

    Fares, Robert L.; Meyers, Jeremy P.; Webber, Michael E.

    2014-01-01

    Highlights: • A model is implemented to describe the dynamic voltage of a vanadium flow battery. • The model is used with optimization to maximize the utility of the battery. • A vanadium flow battery’s value for regulation service is approximately $1500/kW. - Abstract: Building on past work seeking to value emerging energy storage technologies in grid-based applications, this paper introduces a dynamic model-based framework to value a vanadium redox flow battery (VRFB) participating in Texas’ organized electricity market. Our model describes the dynamic behavior of a VRFB system’s voltage and state of charge based on the instantaneous charging or discharging power required from the battery. We formulate an optimization problem that incorporates the model to show the potential value of a VRFB used for frequency regulation service in Texas. The optimization is implemented in Matlab using the large-scale, interior-point, nonlinear optimization algorithm, with the objective function gradient, nonlinear constraint gradients, and Hessian matrix specified analytically. Utilizing market prices and other relevant data from the Electric Reliability Council of Texas (ERCOT), we find that a VRFB system used for frequency regulation service could be worth approximately $1500/kW

  7. Comparison of SH3 and SH2 domain dynamics when expressed alone or in an SH(3+2) construct: the role of protein dynamics in functional regulation.

    Science.gov (United States)

    Engen, J R; Smithgall, T E; Gmeiner, W H; Smith, D L

    1999-04-02

    Protein dynamics play an important role in protein function and regulation of enzymatic activity. To determine how additional interactions with surrounding structure affects local protein dynamics, we have used hydrogen exchange and mass spectrometry to investigate the SH2 and SH3 domains of the protein tyrosine kinase Hck. Exchange rates of isolated Hck SH3 and SH2 domains were compared with rates for the same domains when part of a larger SH(3+2) construct. Increased deuterium incorporation was observed for the SH3 domain in the joint construct, particularly near the SH2 interface and the short sequence that connects SH3 to SH2, implying greater flexibility of SH3 when it is part of SH(3+2). Slow cooperative unfolding of the SH3 domain occurred at the same rate in isolated SH3 as in the SH(3+2) construct, suggesting a functional significance for this unfolding. The SH2 domain displayed relatively smaller changes in flexibility when part of the SH(3+2) construct. These results suggest that the domains influence each other. Further, our results imply a link between functional regulation and structural dynamics of SH3 and SH2 domains. Copyright 1999 Academic Press.

  8. Multiple sources driving the organic matter dynamics in two contrasting tropical mangroves

    International Nuclear Information System (INIS)

    Ray, R.; Shahraki, M.

    2016-01-01

    In this study, we have selected two different mangroves based on their geological, hydrological and climatological variations to investigate the origin (terrestrial, phytobenthos derived, and phytoplankton derived) of dissolved organic carbon (DOC), particulate organic carbon (POC) in the water column and the sedimentary OC using elemental ratios and stable isotopes. Qeshm Island, representing the Iranian mangroves received no attention before this study in terms of DOC, POC biogeochemistry and their sources unlike the Sundarbans (Indian side), the world's largest mangrove system. Slightly higher DOC concentrations in the Iranian mangroves were recorded in our field campaigns between 2011 and 2014, compared to the Sundarbans (315 ± 25 μM vs. 278 ± 42 μM), owing to the longer water residence times, while 9–10 times greater POC concentration (303 ± 37 μM, n = 82) was linked to both suspended load (345 ± 104 mg L"− "1) and high algal production. Yearlong phytoplankton bloom in the mangrove-lined Persian Gulf was reported to be the perennial source of both POC and DOC contributing 80–86% to the DOC and 90–98% to the POC pool. Whereas in the Sundarbans, riverine input contributed 50–58% to the DOC pool and POC composition was regulated by the seasonal litter fall, river discharge and phytoplankton production. Algal derived organic matter (microphytobenthos) represented the maximum contribution (70–76%) to the sedimentary OC at Qeshm Island, while mangrove leaf litters dominated the OC pool in the Indian Sundarbans. Finally, hydrographical settings (i.e. riverine transport) appeared to be the determinant factor in differentiating OM sources in the water column between the dry and wet mangroves. - Highlights: • Sources of OC have been identified and compared between two contrasting mangroves. • Phytoplankton dominated the DOC and POC pool in the Iranian mangroves. • River input contributed half of the total DOC and part of POC in the Indian

  9. Multiple sources driving the organic matter dynamics in two contrasting tropical mangroves

    Energy Technology Data Exchange (ETDEWEB)

    Ray, R., E-mail: raghab.ray@gmail.com [Institut Universitaire Européen de la Mer, UBO, UMR 6539 LEMAR, rue Dumont dUrville, 29280 Plouzane (France); Leibniz Center for Tropical Marine Ecology, Fahrenheitstr. 6, 28359 Bremen (Germany); Shahraki, M. [Leibniz Center for Tropical Marine Ecology, Fahrenheitstr. 6, 28359 Bremen (Germany); Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research, Am Handelshafen 12, 27570 Bremerhaven (Germany)

    2016-11-15

    In this study, we have selected two different mangroves based on their geological, hydrological and climatological variations to investigate the origin (terrestrial, phytobenthos derived, and phytoplankton derived) of dissolved organic carbon (DOC), particulate organic carbon (POC) in the water column and the sedimentary OC using elemental ratios and stable isotopes. Qeshm Island, representing the Iranian mangroves received no attention before this study in terms of DOC, POC biogeochemistry and their sources unlike the Sundarbans (Indian side), the world's largest mangrove system. Slightly higher DOC concentrations in the Iranian mangroves were recorded in our field campaigns between 2011 and 2014, compared to the Sundarbans (315 ± 25 μM vs. 278 ± 42 μM), owing to the longer water residence times, while 9–10 times greater POC concentration (303 ± 37 μM, n = 82) was linked to both suspended load (345 ± 104 mg L{sup −} {sup 1}) and high algal production. Yearlong phytoplankton bloom in the mangrove-lined Persian Gulf was reported to be the perennial source of both POC and DOC contributing 80–86% to the DOC and 90–98% to the POC pool. Whereas in the Sundarbans, riverine input contributed 50–58% to the DOC pool and POC composition was regulated by the seasonal litter fall, river discharge and phytoplankton production. Algal derived organic matter (microphytobenthos) represented the maximum contribution (70–76%) to the sedimentary OC at Qeshm Island, while mangrove leaf litters dominated the OC pool in the Indian Sundarbans. Finally, hydrographical settings (i.e. riverine transport) appeared to be the determinant factor in differentiating OM sources in the water column between the dry and wet mangroves. - Highlights: • Sources of OC have been identified and compared between two contrasting mangroves. • Phytoplankton dominated the DOC and POC pool in the Iranian mangroves. • River input contributed half of the total DOC and part of POC in

  10. Dynamics and regulation of glycolysis-tricarboxylic acid metabolism in the midgut of Spodoptera litura during metamorphosis.

    Science.gov (United States)

    Hu, D; Luo, W; Fan, L F; Liu, F L; Gu, J; Deng, H M; Zhang, C; Huang, L H; Feng, Q L

    2016-04-01

    Significant changes usually take place in the internal metabolism of insects during metamorphosis. The glycolysis-tricarboxylic acid (glycolysis-TCA) pathway is important for energy metabolism. To elucidate its dynamics, the mRNA levels of genes involved in this pathway were examined in the midgut of Spodoptera litura during metamorphosis, and the pyruvate content was quantified. The expression patterns of these genes in response to starvation were examined, and the interaction between protein phosphatase 1 (PP1) and phosphofructokinase (PFK) was studied. The results revealed that the expression or activities of most glycolytic enzymes was down-regulated in prepupae and then recovered in some degree in pupae, and all TCA-related genes were remarkably suppressed in both the prepupae and pupae. Pyruvate was enriched in the pupal midgut. Taken together, these results suggest that insects decrease both glycolysis and TCA in prepupae to save energy and then up-regulate glycolysis but down-regulate TCA in pupae to increase the supply of intermediates for construction of new organs. The expression of all these genes were down-regulated by starvation, indicating that non-feeding during metamorphosis may be a regulator of glycolysis-TCA pathway in the midgut. Importantly, interaction between PP1 and PFK was identified and is suggested to be involved in the regulation of glycolysis. © 2015 The Royal Entomological Society.

  11. Statistical state dynamics-based analysis of the physical mechanisms sustaining and regulating turbulence in Couette flow

    Science.gov (United States)

    Farrell, Brian F.; Ioannou, Petros J.

    2017-08-01

    This paper describes a study of the self-sustaining process in wall turbulence. The study is based on a second order statistical state dynamics model of Couette flow in which the state variables are the streamwise mean flow (first cumulant) and perturbation covariance (second cumulant). This statistical state dynamics model is closed by either setting the third cumulant to zero or by replacing it with a stochastic parametrization. Statistical state dynamics models with this form are referred to as S3T models. S3T models have been shown to self-sustain turbulence with a mean flow and second order perturbation structure similar to that obtained by direct numerical simulation of the equations of motion. The use of a statistical state dynamics model to study the physical mechanisms underlying turbulence has important advantages over the traditional approach of studying the dynamics of individual realizations of turbulence. One advantage is that the analytical structure of S3T statistical state dynamics models isolates the interaction between the mean flow and the perturbation components of the turbulence. Isolation of the interaction between these components reveals how this interaction underlies both the maintenance of the turbulence variance by transfer of energy from the externally driven flow to the perturbation components as well as the enforcement of the observed statistical mean turbulent state by feedback regulation between the mean and perturbation fields. Another advantage of studying turbulence using statistical state dynamics models of S3T form is that the analytical structure of S3T turbulence can be completely characterized. For example, the perturbation component of turbulence in the S3T system is demonstrably maintained by a parametric perturbation growth mechanism in which fluctuation of the mean flow maintains the perturbation field which in turn maintains the mean flow fluctuations in a synergistic interaction. Furthermore, the equilibrium

  12. The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

    Energy Technology Data Exchange (ETDEWEB)

    Blom, Magdalena; Reis, Katarina [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Heldin, Johan [Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala SE-751 22 Uppsala (Sweden); Kreuger, Johan [Department of Medical Cell Biology, Science for Life Laboratory, Uppsala University, SE-751 23 Uppsala (Sweden); Aspenström, Pontus, E-mail: pontus.aspenstrom@ki.se [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden)

    2017-03-15

    RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

  13. The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

    International Nuclear Information System (INIS)

    Blom, Magdalena; Reis, Katarina; Heldin, Johan; Kreuger, Johan; Aspenström, Pontus

    2017-01-01

    RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

  14. Structured association analysis leads to insight into Saccharomyces cerevisiae gene regulation by finding multiple contributing eQTL hotspots associated with functional gene modules.

    Science.gov (United States)

    Curtis, Ross E; Kim, Seyoung; Woolford, John L; Xu, Wenjie; Xing, Eric P

    2013-03-21

    Association analysis using genome-wide expression quantitative trait locus (eQTL) data investigates the effect that genetic variation has on cellular pathways and leads to the discovery of candidate regulators. Traditional analysis of eQTL data via pairwise statistical significance tests or linear regression does not leverage the availability of the structural information of the transcriptome, such as presence of gene networks that reveal correlation and potentially regulatory relationships among the study genes. We employ a new eQTL mapping algorithm, GFlasso, which we have previously developed for sparse structured regression, to reanalyze a genome-wide yeast dataset. GFlasso fully takes into account the dependencies among expression traits to suppress false positives and to enhance the signal/noise ratio. Thus, GFlasso leverages the gene-interaction network to discover the pleiotropic effects of genetic loci that perturb the expression level of multiple (rather than individual) genes, which enables us to gain more power in detecting previously neglected signals that are marginally weak but pleiotropically significant. While eQTL hotspots in yeast have been reported previously as genomic regions controlling multiple genes, our analysis reveals additional novel eQTL hotspots and, more interestingly, uncovers groups of multiple contributing eQTL hotspots that affect the expression level of functional gene modules. To our knowledge, our study is the first to report this type of gene regulation stemming from multiple eQTL hotspots. Additionally, we report the results from in-depth bioinformatics analysis for three groups of these eQTL hotspots: ribosome biogenesis, telomere silencing, and retrotransposon biology. We suggest candidate regulators for the functional gene modules that map to each group of hotspots. Not only do we find that many of these candidate regulators contain mutations in the promoter and coding regions of the genes, in the case of the Ribi group

  15. DMPD: New insights into NF-kappaB regulation and function. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18775672 New insights into NF-kappaB regulation and function. Sun SC, Ley SC. Trend...ction. PubmedID 18775672 Title New insights into NF-kappaB regulation and function....s Immunol. 2008 Oct;29(10):469-78. Epub 2008 Sep 3. (.png) (.svg) (.html) (.csml) Show New insights into NF-kappaB regulation and fun

  16. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  17. DMPD: Receptor tyrosine kinases and the regulation of macrophage activation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14726496 Receptor tyrosine kinases and the regulation of macrophage activation. Cor...osine kinases and the regulation of macrophage activation. PubmedID 14726496 Title Receptor tyrosine...rell PH, Morrison AC, Lutz MA. J Leukoc Biol. 2004 May;75(5):731-7. Epub 2004 Jan 14. (.png) (.svg) (.html) (.csml) Show Receptor tyr

  18. Complex Interplay between FleQ, Cyclic Diguanylate and Multiple σ Factors Coordinately Regulates Flagellar Motility and Biofilm Development in Pseudomonas putida.

    Directory of Open Access Journals (Sweden)

    Alicia Jiménez-Fernández

    Full Text Available Most bacteria alternate between a free living planktonic lifestyle and the formation of structured surface-associated communities named biofilms. The transition between these two lifestyles requires a precise and timely regulation of the factors involved in each of the stages that has been likened to a developmental process. Here we characterize the involvement of the transcriptional regulator FleQ and the second messenger cyclic diguanylate in the coordinate regulation of multiple functions related to motility and surface colonization in Pseudomonas putida. Disruption of fleQ caused strong defects in flagellar motility, biofilm formation and surface attachment, and the ability of this mutation to suppress multiple biofilm-related phenotypes associated to cyclic diguanylate overproduction suggests that FleQ mediates cyclic diguanylate signaling critical to biofilm growth. We have constructed a library containing 94 promoters potentially involved in motility and biofilm development fused to gfp and lacZ, screened this library for FleQ and cyclic diguanylate regulation, and assessed the involvement of alternative σ factors σN and FliA in the transcription of FleQ-regulated promoters. Our results suggest a dual mode of action for FleQ. Low cyclic diguanylate levels favor FleQ interaction with σN-dependent promoters to activate the flagellar cascade, encompassing the flagellar cluster and additional genes involved in cyclic diguanylate metabolism, signal transduction and gene regulation. On the other hand, characterization of the FleQ-regulated σN- and FliA-independent PlapA and PbcsD promoters revealed two disparate regulatory mechanisms leading to a similar outcome: the synthesis of biofilm matrix components in response to increased cyclic diguanylate levels.

  19. Dynamics of study strategies and teacher regulation in virtual patient learning activities: a cross sectional survey.

    Science.gov (United States)

    Edelbring, Samuel; Wahlström, Rolf

    2016-04-23

    Students' self-regulated learning becomes essential with increased use of exploratory web-based activities such as virtual patients (VPs). The purpose was to investigate the interplay between students' self-regulated learning strategies and perceived benefit in VP learning activities. A cross-sectional study (n = 150) comparing students' study strategies and perceived benefit of a virtual patient learning activity in a clinical clerkship preparatory course. Teacher regulation varied among three settings and was classified from shared to strong. These settings were compared regarding their respective relations between regulation strategies and perceived benefit of the virtual patient activity. Self-regulation learning strategy was generally associated with perceived benefit of the VP activities (rho 0.27, p strategies can increase the value of flexible web-based learning resources to students.

  20. Evolution-development congruence in pattern formation dynamics: Bifurcations in gene expression and regulation of networks structures.

    Science.gov (United States)

    Kohsokabe, Takahiro; Kaneko, Kunihiko

    2016-01-01

    Search for possible relationships between phylogeny and ontogeny is important in evolutionary-developmental biology. Here we uncover such relationships by numerical evolution and unveil their origin in terms of dynamical systems theory. By representing developmental dynamics of spatially located cells with gene expression dynamics with cell-to-cell interaction under external morphogen gradient, gene regulation networks are evolved under mutation and selection with the fitness to approach a prescribed spatial pattern of expressed genes. For most numerical evolution experiments, evolution of pattern over generations and development of pattern by an evolved network exhibit remarkable congruence. Both in the evolution and development pattern changes consist of several epochs where stripes are formed in a short time, while for other temporal regimes, pattern hardly changes. In evolution, these quasi-stationary regimes are generations needed to hit relevant mutations, while in development, they are due to some gene expression that varies slowly and controls the pattern change. The morphogenesis is regulated by combinations of feedback or feedforward regulations, where the upstream feedforward network reads the external morphogen gradient, and generates a pattern used as a boundary condition for the later patterns. The ordering from up to downstream is common in evolution and development, while the successive epochal changes in development and evolution are represented as common bifurcations in dynamical-systems theory, which lead to the evolution-development congruence. Mechanism of exceptional violation of the congruence is also unveiled. Our results provide a new look on developmental stages, punctuated equilibrium, developmental bottlenecks, and evolutionary acquisition of novelty in morphogenesis. © 2015 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution Published by Wiley Periodicals, Inc.

  1. Dynamic Interaction of Stress Granules, DDX3X, and IKK-α Mediates Multiple Functions in Hepatitis C Virus Infection.

    Science.gov (United States)

    Pène, Véronique; Li, Qisheng; Sodroski, Catherine; Hsu, Ching-Sheng; Liang, T Jake

    2015-05-01

    The ubiquitous ATP-dependent RNA helicase DDX3X is involved in many cellular functions, including innate immunity, and is a pivotal host factor for hepatitis C virus (HCV) infection. Recently, we showed that DDX3X specifically recognizes the HCV 3' untranslated region (UTR), leading to the activation of IKK-α and a cascade of lipogenic signaling to facilitate lipid droplet biogenesis and viral assembly (Q. Li, V. Pene, S. Krishnamurthy, H. Cha, and T. J. Liang, Nat Med 19:722-729, 2013, http://dx.doi.org/10.1038/nm.3190). The interaction of DDX3X with HCV core protein seems to be dispensable for its proviral role. In this study, through systematic imaging and biochemical and virologic approaches, we identified a dynamic association between DDX3X and various cellular compartments and viral elements mediating multiple functions of DDX3X in productive HCV infection. Upon HCV infection, the HCV 3'UTR interacts with DDX3X and IKK-α, which redistribute to speckle-like cytoplasmic structures shown to be stress granules (SGs). As viral proteins accumulate in infected cells, DDX3X granules together with SG-associated proteins redistribute and colocalize with HCV core protein around lipid droplets (LDs). IKK-α, however, does not relocate to the LD but translocates to the nucleus. In HCV-infected cells, various HCV nonstructural proteins also interact or colocalize with DDX3X in close proximity to SGs and LDs, consistent with the tight juxtaposition of the replication complex and the assembly site at the surface of LDs. Short interfering RNA (siRNA)-mediated silencing of DDX3X and multiple SG components markedly inhibits HCV infection. Our data suggest that DDX3X initiates a multifaceted cellular program involving dynamic associations with HCV RNA and proteins, IKK-α, SG, and LD surfaces for its crucial role in the HCV life cycle. IMPORTANCE DDX3X is a proviral host factor for HCV infection. Recently, we showed that DDX3X binds to the HCV 3'UTR, activating IKK-α and

  2. Regulation-Structured Dynamic Metabolic Model Provides a Potential Mechanism for Delayed Enzyme Response in Denitrification Process

    Energy Technology Data Exchange (ETDEWEB)

    Song, Hyun-Seob; Thomas, Dennis G.; Stegen, James C.; Li, Minjing; Liu, Chongxuan; Song, Xuehang; Chen, Xingyuan; Fredrickson, Jim K.; Zachara, John M.; Scheibe, Timothy D.

    2017-09-29

    In a recent study of denitrification dynamics in hyporheic zone sediments, we observed a significant time lag (up to several days) in enzymatic response to the changes in substrate concentration. To explore an underlying mechanism and understand the interactive dynamics between enzymes and nutrients, we developed a trait-based model that associates a community’s traits with functional enzymes, instead of typically used species guilds (or functional guilds). This enzyme-based formulation allows to collectively describe biogeochemical functions of microbial communities without directly parameterizing the dynamics of species guilds, therefore being scalable to complex communities. As a key component of modeling, we accounted for microbial regulation occurring through transcriptional and translational processes, the dynamics of which was parameterized based on the temporal profiles of enzyme concentrations measured using a new signature peptide-based method. The simulation results using the resulting model showed several days of a time lag in enzymatic responses as observed in experiments. Further, the model showed that the delayed enzymatic reactions could be primarily controlled by transcriptional responses and that the dynamics of transcripts and enzymes are closely correlated. The developed model can serve as a useful tool for predicting biogeochemical processes in natural environments, either independently or through integration with hydrologic flow simulators.

  3. [Chaotic dynamic process of multiple organs dysfunction syndrome and the regulatory function of shenqin liquid on it].

    Science.gov (United States)

    Liang, Jun-Xiong; Weng, Shu-He; Chen, Jing-He

    2008-07-01

    To explore the chaotic dynamic process of multiple organs dysfunction syndrome (MODS) and the regulatory effect of Shenqin Liquid (SQL), a Chinese herbal liquid preparation with the action of purging and qi-tonifying. Eighty SD rats were divided into 4 groups, and were given suspension of zymosan A and paraffine (1 mL/kg) by peritoneal injection except for those in the blank control group to set up the multiple organs dysfunction syndrome (MODS) model. Low and high doses SQL were administered twice at the doses of 30 and 60 g/kg of SQL respectively at an interval of 8 h per day before modeling. Serum concentration of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) in MODS model animals were tested diachronically, eg. 12, 6 h before modeling, during modeling, 6 and 12 h after modeling, and then the mathematic models were built up with compartment analysis. Lyapunov exponents (LE) of the mathematic models were calculated to evaluate their chaotic characteristics of movement and the degree of chaos was ascertained with the correlation dimension (CD). The serum levels of TNF-alpha and NO were significantly higher than those in the bland control group at modeling, 6, and 12 h after modeling (P SQL were significantly lower than the model group (P SQL was significantly lower than that in the low dose group (P 0 respectively; in the low dose and high dose SQL treated groups, CD was 0.517 and 0.653 respectively and LE >0. CD of NO movement in the blank control group was 0.670 and with LE 0; in the low dose SQL group, 0.574 and in the high dose SQL group 0.850, and LE SQL can intervene the movement of TNF-alpha and NO, decrease the complexity of their chaotic movement, and make them return back to a stable state.

  4. Effects of multiple resistive shells and transient electromagnetic torque on the dynamics of mode locking in reversed field pinch plasmas

    International Nuclear Information System (INIS)

    Guo, S.C.; Chu, M.S.

    2002-01-01

    The effects of multiple resistive shells and transient electromagnetic torque on the dynamics of mode locking in the reversed field pinch (RFP) plasmas are studied. Most RFP machines are equipped with one or more metal shells outside of the vacuum vessel. These shells have finite resistivities. The eddy currents induced in each of the shells contribute to the braking electromagnetic (EM) torque which slows down the plasma rotation. In this work we study the electromagnetic torque acting on the plasma (tearing) modes produced by a system of resistive shells. These shells may consist of several nested thin shells or several thin shells enclosed within a thick shell. The dynamics of the plasma mode is investigated by balancing the EM torque from the resistive shells with the plasma viscous torque. Both the steady state theory and the time-dependent theory are developed. The steady state theory is shown to provide an accurate account of the resultant EM torque if (dω/dt)ω -2 <<1 and the time scale of interest is much longer than the response (L/R) time of the shell. Otherwise, the transient theory should be adopted. As applications, the steady state theory is used to evaluate the changes of the EM torque response from the resistive shells in two variants of two RFP machines: (1) modification from Reversed Field Experiment (RFX) [Gnesotto et al., Fusion Eng. Des. 25, 335 (1995)] to the modified RFX: both of them are equipped with one thin shell plus one thick shell; (2) modification from Extrap T2 to Extrap T2R [Brunsell et al., Plasma Phys. Controlled Fusion 43, 1457 (2001)]: both of them are equipped with two thin shells. The transient theory has been applied numerically to study the time evolution of the EM torque during the unlocking of a locked tearing mode in the modified RFX

  5. Steam drum level dynamics in a multiple loop natural circulation system of a pressure-tube type boiling water reactor

    International Nuclear Information System (INIS)

    Jain, Vikas; Kulkarni, P.P.; Nayak, A.K.; Vijayan, P.K.; Saha, D.; Sinha, R.K.

    2011-01-01

    Highlights: → We have highlighted the problem of drum level dynamics in a multiple loop type NC system using RELAP5 code. → The need of interconnections in steam and liquid spaces close to drum is established. → The steam space interconnections equalize pressure and liquid space interconnections equalize level. → With this scheme, the system can withstand anomalous conditions. → However, the controller is found to be inevitable for inventory balance. - Abstract: Advanced Heavy Water Reactor (AHWR) is a pressure tube type boiling water reactor employing natural circulation as the mode of heat removal under all the operating conditions. Main heat transport system (MHTS) of AHWR is essentially a multi-loop natural circulation system with all the loops connected to each other. Each loop of MHTS has a steam drum that provides for gravity based steam-water separation. Steam drum level is a very critical parameter especially in multi-loop natural circulation systems as large departures from the set point may lead to ineffective separation of steam-water or may affect the driving head. However, such a system is susceptible to steam drum level anomalies under postulated asymmetrical operating conditions among the different quadrants of the core like feedwater flow distribution anomaly among the steam drums or power anomaly among the core quadrants. Analyses were carried out to probe such scenarios and unravel the underlying dynamics of steam drum level using system code RELAP5/Mod3.2. In addition, a scheme to obviate such problem in a passive manner without dependence on level controller was examined. It was concluded that steam drums need to be connected in the liquid as well as steam space to make the system tolerant to asymmetrical operating conditions.

  6. An integrated mechanism of pediatric pseudotumor cerebri syndrome: evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics.

    Science.gov (United States)

    Sheldon, Claire A; Kwon, Young Joon; Liu, Grant T; McCormack, Shana E

    2015-02-01

    Pseudotumor cerebri syndrome (PTCS) is defined by the presence of elevated intracranial pressure (ICP) in the setting of normal brain parenchyma and cerebrospinal fluid (CSF). Headache, vision changes, and papilledema are common presenting features. Up to 10% of appropriately treated patients may experience permanent visual loss. The mechanism(s) underlying PTCS is unknown. PTCS occurs in association with a variety of conditions, including kidney disease, obesity, and adrenal insufficiency, suggesting endocrine and/or metabolic derangements may occur. Recent studies suggest that fluid and electrolyte balance in renal epithelia is regulated by a complex interaction of metabolic and hormonal factors; these cells share many of the same features as the choroid plexus cells in the central nervous system (CNS) responsible for regulation of CSF dynamics. Thus, we posit that similar factors may influence CSF dynamics in both types of fluid-sensitive tissues. Specifically, we hypothesize that, in patients with PTCS, mitochondrial metabolites (glutamate, succinate) and steroid hormones (cortisol, aldosterone) regulate CSF production and/or absorption. In this integrated mechanism review, we consider the clinical and molecular evidence for each metabolite and hormone in turn. We illustrate how related intracellular signaling cascades may converge in the choroid plexus, drawing on evidence from functionally similar tissues.

  7. Shaping the tracks : Regulation of microtubule dynamics by kinesins KIF21A and KIF21B

    NARCIS (Netherlands)

    van Riel, W.E.|info:eu-repo/dai/nl/338772634

    2016-01-01

    Control of microtubule dynamics is important for cell morphogenesis. Kinesins, motor proteins known to function in cargo transport, were recently also implicated in altering the microtubule network. Several kinesins are described to cause microtubule network reorganization or stabilization, either

  8. New Approach for Nuclear Safety and Regulation - Application of Complexity Theory and System Dynamics

    International Nuclear Information System (INIS)

    Choi, Kwang Sik; Choi, Young Sung; Han, Kyu Hyun; Kim, Do Hyoung

    2007-01-01

    The methodology being used today for assuring nuclear safety is based on analytic approaches. In the 21st century, holistic approaches are increasingly used over traditional analytic method that is based on reductionism. Presently, it leads to interest in complexity theory or system dynamics. In this paper, we review global academic trends, social environments, concept of nuclear safety and regulatory frameworks for nuclear safety. We propose a new safety paradigm and also regulatory approach using holistic approach and system dynamics now in fashion

  9. Ab initio multiple spawning dynamics study of dimethylnitramine and dimethylnitramine-Fe complex to model their ultrafast nonadiabatic chemistry.

    Science.gov (United States)

    Bera, Anupam; Ghosh, Jayanta; Bhattacharya, Atanu

    2017-07-28

    Conical intersections are now firmly established to be the key features in the excited electronic state processes of polyatomic energetic molecules. In the present work, we have explored conical intersection-mediated nonadiabatic chemical dynamics of a simple analogue nitramine molecule, dimethylnitramine (DMNA, containing one N-NO 2 energetic group), and its complex with an iron atom (DMNA-Fe). For this task, we have used the ab initio multiple spawning (AIMS) dynamics simulation at the state averaged-complete active space self-consistent field(8,5)/6-31G(d) level of theory. We have found that DMNA relaxes back to the ground (S 0 ) state following electronic excitation to the S 1 excited state [which is an (n,π*) excited state] with a time constant of approximately 40 fs. This AIMS result is in very good agreement with the previous surface hopping-result and femtosecond laser spectroscopy result. DMNA does not dissociate during this fast internal conversion from the S 1 to the S 0 state. DMNA-Fe also undergoes extremely fast relaxation from the upper S 1 state to the S 0 state; however, this relaxation pathway is dissociative in nature. DMNA-Fe undergoes initial Fe-O, N-O, and N-N bond dissociations during relaxation from the upper S 1 state to the ground S 0 state through the respective conical intersection. The AIMS simulation reveals the branching ratio of these three channels as N-N:Fe-O:N-O = 6:3:1 (based on 100 independent simulations). Furthermore, the AIMS simulation reveals that the Fe-O bond dissociation channel exhibits the fastest (time constant 24 fs) relaxation, while the N-N bond dissociation pathway features the slowest (time constant 128 fs) relaxation. An intermediate time constant (30 fs) is found for the N-O bond dissociation channel. This is the first nonadiabatic chemical dynamics study of metal-contained energetic molecules through conical intersections.

  10. Ab initio multiple spawning dynamics study of dimethylnitramine and dimethylnitramine-Fe complex to model their ultrafast nonadiabatic chemistry

    Science.gov (United States)

    Bera, Anupam; Ghosh, Jayanta; Bhattacharya, Atanu

    2017-07-01

    Conical intersections are now firmly established to be the key features in the excited electronic state processes of polyatomic energetic molecules. In the present work, we have explored conical intersection-mediated nonadiabatic chemical dynamics of a simple analogue nitramine molecule, dimethylnitramine (DMNA, containing one N-NO2 energetic group), and its complex with an iron atom (DMNA-Fe). For this task, we have used the ab initio multiple spawning (AIMS) dynamics simulation at the state averaged-complete active space self-consistent field(8,5)/6-31G(d) level of theory. We have found that DMNA relaxes back to the ground (S0) state following electronic excitation to the S1 excited state [which is an (n,π*) excited state] with a time constant of approximately 40 fs. This AIMS result is in very good agreement with the previous surface hopping-result and femtosecond laser spectroscopy result. DMNA does not dissociate during this fast internal conversion from the S1 to the S0 state. DMNA-Fe also undergoes extremely fast relaxation from the upper S1 state to the S0 state; however, this relaxation pathway is dissociative in nature. DMNA-Fe undergoes initial Fe-O, N-O, and N-N bond dissociations during relaxation from the upper S1 state to the ground S0 state through the respective conical intersection. The AIMS simulation reveals the branching ratio of these three channels as N-N:Fe-O:N-O = 6:3:1 (based on 100 independent simulations). Furthermore, the AIMS simulation reveals that the Fe-O bond dissociation channel exhibits the fastest (time constant 24 fs) relaxation, while the N-N bond dissociation pathway features the slowest (time constant 128 fs) relaxation. An intermediate time constant (30 fs) is found for the N-O bond dissociation channel. This is the first nonadiabatic chemical dynamics study of metal-contained energetic molecules through conical intersections.

  11. Exact solutions in the dynamics of alternating open chains of spins s = 1/2 with the XY Hamiltonian and their application to problems of multiple-quantum dynamics and quantum information theory

    International Nuclear Information System (INIS)

    Kuznetsova, E. I.; Fel'dman, E. B.

    2006-01-01

    A method for exactly diagonalizing the XY Hamiltonian of an alternating open chain of spins s = 1/2 has been proposed on the basis of the Jordan-Wigner transformation and analysis of the dynamics of spinless fermions. The multiple-quantum spin dynamics of alternating open chains at high temperatures has been analyzed and the intensities of multiple-quantum coherences have been calculated. The problem of the transfer of a quantum state from one end of the alternating chain to the other is studied. It has been shown that the ideal transfer of qubits is possible in alternating chains with a larger number of spins than that in homogeneous chains

  12. Dynamic Model of Kaplan Turbine Regulating System Suitable for Power System Analysis

    OpenAIRE

    Zhao, Jie; Wang, Li; Liu, Dichen; Wang, Jun; Zhao, Yu; Liu, Tian; Wang, Haoyu

    2015-01-01

    Accurate modeling of Kaplan turbine regulating system is of great significance for grid security and stability analysis. In this paper, Kaplan turbine regulating system model is divided into the governor system model, the blade control system model, and the turbine and water diversion system model. The Kaplan turbine has its particularity, and the on-cam relationship between the wicket gate opening and the runner blade angle under a certain water head on the whole range was obtained by high-o...

  13. Transnational Dynamics Amid Poor Regulations: Taiwan’s Asbestos Ban Actions and Experiences

    Directory of Open Access Journals (Sweden)

    Harry Yi-Jui Wu

    2017-10-01

    Full Text Available This article describes the history of the asbestos use regulation process in Taiwan and the associated factors leading to its total ban in 2018. Despite the long history of asbestos mining and manufacturing since the Japanese colonial period, attempts to understand the impact of asbestos on the health of the population and to control its use did not emerge until the early 1980s. We attempted to investigate the driving forces and obstructions involved in asbestos regulations by reviewing available public sources and scientific journal articles and conducting interviews with key propagators of the asbestos regulation and ban. Correlation between asbestos exposure and asbestos-related diseases has already been established; however, authorities have been unable to effectively regulate the extensive application of asbestos in various light industries that support economic growth since the 1960s. More stringent regulations on asbestos use in industries and an eventual ban were caused indirectly by appeals made by visionary scholars and healthcare professionals but also due to the subsidence of asbestos-related industries. With the elucidation of factors that affect asbestos regulation and ban, a thorough long-term healthcare plan for the neglected victims of asbestos-related diseases and upstream measures for policy change must be developed.

  14. Acute and chronic glucocorticoid treatments regulate astrocyte-enriched mRNAs in multiple brain regions in vivo

    Directory of Open Access Journals (Sweden)

    Bradley S. Carter

    2013-08-01

    Full Text Available Previous studies have primarily interpreted gene expression regulation by glucocorticoids in the brain in terms of impact on neurons; however, less is known about the corresponding impact of glucocorticoids on glia and specifically astrocytes in vivo. Recent microarray experiments have identified glucocorticoid-sensitive mRNAs in primary astrocyte cell culture, including a number of mRNAs that have reported astrocyte-enriched expression patterns relative to other brain cell types. Here, we have tested whether elevations of glucocorticoids regulate a subset of these mRNAs in vivo following acute and chronic corticosterone exposure in adult mice. Acute corticosterone exposure was achieved by a single injection of 10 mg/kg corticosterone, and tissue samples were harvested two hours post-injection. Chronic corticosterone exposure was achieved by administering 10 mg/mL corticosterone via drinking water for two weeks. Gene expression was then assessed in two brain regions associated with glucocorticoid action (prefrontal cortex and hippocampus by qPCR and by in situ hybridization. The majority of measured mRNAs regulated by glucocorticoids in astrocytes in vitro were similarly regulated by acute and/or chronic glucocorticoid exposure in vivo. In addition, the expression levels for mRNAs regulated in at least one corticosterone exposure condition (acute/chronic demonstrated moderate positive correlation between the two conditions by brain region. In situ hybridization analyses suggest that select mRNAs are regulated by chronic corticosterone exposure specifically in astroctyes based on (1 similar general expression patterns between corticosterone-treated and vehicle-treated animals and (2 similar expression patterns to the pan-astrocyte marker Aldh1l1. Our findings demonstrate that glucocorticoids regulate astrocyte-enriched mRNAs in vivo and suggest that glucocorticoids regulate gene expression in the brain in a cell type-dependent fashion.

  15. Neural Dynamics of Multiple Object Processing in Mild Cognitive Impairment and Alzheimer's Disease: Future Early Diagnostic Biomarkers?

    Science.gov (United States)

    Bagattini, Chiara; Mazza, Veronica; Panizza, Laura; Ferrari, Clarissa; Bonomini, Cristina; Brignani, Debora

    2017-01-01

    The aim of this study was to investigate the behavioral and electrophysiological dynamics of multiple object processing (MOP) in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to test whether its neural signatures may represent reliable diagnostic biomarkers. Behavioral performance and event-related potentials [N2pc and contralateral delay activity (CDA)] were measured in AD, MCI, and healthy controls during a MOP task, which consisted in enumerating a variable number of targets presented among distractors. AD patients showed an overall decline in accuracy for both small and large target quantities, whereas in MCI patients, only enumeration of large quantities was impaired. N2pc, a neural marker of attentive individuation, was spared in both AD and MCI patients. In contrast, CDA, which indexes visual short term memory abilities, was altered in both groups of patients, with a non-linear pattern of amplitude modulation along the continuum of the disease: a reduction in AD and an increase in MCI. These results indicate that AD pathology shows a progressive decline in MOP, which is associated to the decay of visual short-term memory mechanisms. Crucially, CDA may be considered as a useful neural signature both to distinguish between healthy and pathological aging and to characterize the different stages along the AD continuum, possibly becoming a reliable candidate for an early diagnostic biomarker of AD pathology.

  16. GENESIS 1.1: A hybrid-parallel molecular dynamics simulator with enhanced sampling algorithms on multiple computational platforms.

    Science.gov (United States)

    Kobayashi, Chigusa; Jung, Jaewoon; Matsunaga, Yasuhiro; Mori, Takaharu; Ando, Tadashi; Tamura, Koichi; Kamiya, Motoshi; Sugita, Yuji

    2017-09-30

    GENeralized-Ensemble SImulation System (GENESIS) is a software package for molecular dynamics (MD) simulation of biological systems. It is designed to extend limitations in system size and accessible time scale by adopting highly parallelized schemes and enhanced conformational sampling algorithms. In this new version, GENESIS 1.1, new functions and advanced algorithms have been added. The all-atom and coarse-grained potential energy functions used in AMBER and GROMACS packages now become available in addition to CHARMM energy functions. The performance of MD simulations has been greatly improved by further optimization, multiple time-step integration, and hybrid (CPU + GPU) computing. The string method and replica-exchange umbrella sampling with flexible collective variable choice are used for finding the minimum free-energy pathway and obtaining free-energy profiles for conformational changes of a macromolecule. These new features increase the usefulness and power of GENESIS for modeling and simulation in biological research. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. A Refined Teaching-Learning Based Optimization Algorithm for Dynamic Economic Dispatch of Integrated Multiple Fuel and Wind Power Plants

    Directory of Open Access Journals (Sweden)

    Umamaheswari Krishnasamy

    2014-01-01

    Full Text Available Dynamic economic dispatch problem (DEDP for a multiple fuel power plant is a nonlinear and nonsmooth optimization problem when valve-point effects, multifuel effects, and ramp-rate limits are considered. Additionally wind energy is also integrated with the DEDP to supply the load for effective utilization of the renewable energy. Since the wind power may not be predicted, a radial basis function network (RBFN is presented to forecast a one-hour-ahead wind power to plan and ensure a reliable power supply. In this paper, a refined teaching-learning based optimization (TLBO is applied to minimize the overall cost of operation of wind-thermal power system. The TLBO is refined by integrating the sequential quadratic programming (SQP method to fine-tune the better solutions whenever discovered by the former method. To demonstrate the effectiveness of the proposed hybrid TLBO-SQP method, a standard DEDP and one practical DEDP with wind power forecasted are tested based on the practical information of wind speed. Simulation results validate the proposed methodology which is reasonable by ensuring quality solution throughout the scheduling horizon for secure operation of the system.

  18. Dynamic Testing of Analogical Reasoning in 5- to 6-Year-Olds : Multiple-Choice Versus Constructed-Response Training Items

    NARCIS (Netherlands)

    Stevenson, C.E.; Heiser, W.J.; Resing, W.C.M.

    2016-01-01

    Multiple-choice (MC) analogy items are often used in cognitive assessment. However, in dynamic testing, where the aim is to provide insight into potential for learning and the learning process, constructed-response (CR) items may be of benefit. This study investigated whether training with CR or MC

  19. Quantitative Analysis of Bioactive Compounds from Aromatic Plants by Means of Dynamic Headspace Extraction and Multiple Headspace Extraction-Gas Chromatography-Mass Spectrometry

    NARCIS (Netherlands)

    Omar, Jone; Olivares, Maitane; Alonso, Ibone; Vallejo, Asier; Aizpurua-Olaizola, Oier; Etxebarria, Nestor

    2016-01-01

    Seven monoterpenes in 4 aromatic plants (sage, cardamom, lavender, and rosemary) were quantified in liquid extracts and directly in solid samples by means of dynamic headspace-gas chromatography-mass spectrometry (DHS-GC-MS) and multiple headspace extraction-gas chromatography-mass spectrometry

  20. Dynamic Testing of Analogical Reasoning in 5- to 6-Year-Olds: Multiple-Choice versus Constructed-Response Training Items

    Science.gov (United States)

    Stevenson, Claire E.; Heiser, Willem J.; Resing, Wilma C. M.

    2016-01-01

    Multiple-choice (MC) analogy items are often used in cognitive assessment. However, in dynamic testing, where the aim is to provide insight into potential for learning and the learning process, constructed-response (CR) items may be of benefit. This study investigated whether training with CR or MC items leads to differences in the strategy…